p38 MAPK信号转导通路在蛛网膜下腔出血后脑血管痉挛中作用的实验研究
摘要
本课题通过建立新西兰大白兔蛛网膜下腔二次注血模型,主要研究以下内容：(1)SAH后p38MAPK在血管壁组织中的表达及其时相；(2)给予p38MAPK特异性抑制剂SB203580对SAH后血管壁炎症反应的抑制作用；(3)给予p38MAPK特异性抑制剂SB203580对SAH后血管内皮细胞凋亡的抑制作用。
第一部分p38MAPK信号转导通路在蛛网膜下腔出血后脑血管痉挛中的作用
目的：细胞内信号转导通路是近年蛛网膜下腔出血后脑血管痉挛发病机制中的研究热点。p38MAPK信号通路广泛参与组织细胞的生长、存活、分化、凋亡及炎症反应等病理生理过程。本实验旨在研究实验性SAH后p38MAPK在血管壁组织中的表达及其时相,以及应用p38MAPK抑制剂SB203580后脑血管痉挛是否得到改善。
方法：第一组实验中,48例成年新西兰兔,随机分为4组：对照组(n=6),SAH3天组(n=6),SAH5天组(n=6),SAH7天组(n=6)。采用SAH模型为枕大池二次注血模型。分别于第一次注血后第3、5、7天,处死SAH组动物,取基底动脉标本。第二组实验中,24例成年新西兰兔,随机分为4组：对照组(n=6),SAH组(n=6),SAH+DMSO组(n=6),SAH+SB203580组(n=6)。动物模型同第一组实验,于第7天处死所有动物,获得基底动脉标本。Western Blot法测定血管壁组织中总p38MAPK、磷酸化p38MAPK (p-p38MAPK)、总ATF2及磷酸化ATF2的水平。活体灌注后HE染色测量基底动脉管腔面积。
结果：(1)SAH后兔基底动脉p-p38MAPK与P-ATF2的水平在SAH后第3天即有明显升高,第5天达到高峰,第7天略有回落；(2) SB203580可明显降低SAH后p38MAPK、ATF2磷酸化水平,抑制了p38MAPK通路的活性；(3)SB203580明显缓解了脑血管痉挛。
结论：p38MAPK的活性在SAH后痉挛血管中明显上调,其介导的信号通路在SAH后脑血管痉挛的病理过程中起重要作用。
第二部分p38MAPK信号转导通路对蛛网膜下腔出血后脑血管壁炎症反应的作用
目的：血管壁的炎症反应是导致蛛网膜下腔出血后脑血管痉挛的发生以及维持的重要因素。p38MAPK信号通路是参与调控组织细胞炎症反应的重要通路。本实验旨在研究应用p38MAPK特异性抑制齐(?)SB203580对实验性SAH后基底动脉血管壁组织炎症反应的抑制作用。
方法：48例成年新西兰兔,随机分为4组：对照组(n=6),SAH组(n=6),SAH+DMSO组(n=6),SAH+SB203580组(n=6)。动物模型同第一组实验,于第一次注血后第7天,处死所有动物,获得基底动脉标本。RT-PCR法测定血管壁组织中炎性细胞因子IL-1β、TNF-α、ICAM-1、VCAM-1的转录活性,免疫组化法观察血管壁组织中炎症细胞相关抗原CD4、CD68、MPO的表达。
结果：SAH后第7天兔基底动脉组织中炎性细胞因子IL-1β、TNF-α、ICAM-1、 VCAM-1的转录活性均明显增高,炎症细胞相关抗原CD4、CD68、MPO的表达增多。SB203580可明显降低SAH后血管壁组织炎性细胞因子的转录活性和炎症细胞相关抗原的表达。
结论：SAH后血管壁组织存在明显的炎症反应,可能与p38MAPK信号通路的活化有关,应用p38MAPK特异性抑制剂SB203580可明显抑制血管壁炎症反应水平。
第三部分p38MAPK信号转导通路与蛛网膜下腔出血后的脑血管内皮细胞凋亡
目的：血管内皮细胞凋亡是蛛网膜下腔出血后脑血管痉挛发病机制中的重要环节。p38MAPK信号通路是调控组织细胞凋亡的重要通路。本实验旨在研究应用p38MAPK特异性抑制剂SB203580对实验性SAH后基底动脉血管内皮细胞凋亡的抑制作用。
方法：48只成年新西兰兔,随机分为4组：对照组(n=6),SAH组(n=6),SAH+DMSO组(n=6),SAH+SB203580组(n=6)。动物模型同第一组实验,于第一次注血后第7天,处死所有动物,获得基底动脉标本。Western-blot法测定血管壁组织中半胱氨酸蛋白酶-3(caspase-3)的表达,TUNEL法观察血管内皮细胞凋亡情况。
结果：SAH后第7天兔基底动脉组织中;aspase-3的表达明显增高,TUNEL法染色血管内皮细胞阳性染色明显增多。SB203580可明显降低SAH后血管壁组织中caspase-3的活性并抑制血管内皮细胞的凋亡。
结论：SAH后血管内皮细胞存在明显的凋亡,可能与p38MAPK信号通路的活化有关,应用p38MAPK特异性抑制剂SB203580可明显抑制SAH后血管内皮细胞的凋亡。
PART Ⅰ:Potential role of p38MAPK pathway in cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits
Objective:Previous studies have demonstrated signal transduction pathways play a critical role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage and p38MAPK pathway has been shown to be involved in numerous physiological processes, such as cell proliferation,cell survival, apoptosis, inflammation, and embryonic development. This work was conducted to investigate the role of p38MAPK on cerebral vasospasm in a rabbit model of SAH.
Methods:In experiment1,24rabbits were assigned randomly to four groups:control, SAH day3, SAH day5, and SAH day7groups,and were killed on days3,5, and7. The time course of the total p38MAPK,p-p38MAPK,total ATF2and p-ATF2activation in the basilar artery after SAH was analyzed by Wester blot.In experiment2,24rabbits were assigned randomly to four groups:control, SAH, SAH+DMSO,SAH+SB203580,and were killed on day7. The blood vessel cross-sectional area was measured by hematoxylin-eosin staining.
Results:As a result, the elevated expression of activated p-p38MAPK and p-ATF2was detected in the basilar artery after SAH from day3,peaked on day5. After SB203580intracisternal administration, the level of p-p38MAPK and p-ATF2were decreased and the vasospasm was markedly attenuated in the basilar arteries.
Conclusion:p38MAPK pathway was activated in the arterial wall after SAH and contribute to vasospasm development. Administration of p38MAPK inhibitor may attenuate cerebral vasospasm in a rabbit model of SAH.
PART Ⅱ:Potential role of p38MAPK pathway in the inflammatory reaction after experimental subarachnoid hemorrhage
Objective:Inflammatory recaction is involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was conducted to examine whether SB203580,a p38MAPK inhibitor,would suppress inflammatory recaction after experimental SAH.
Methods:48rabbits were assigned randomly to four groups:control, SAH, SAH+DMSO,SAH+SB203580,and were killed on day7. The gene expression levels of cytokines and adhesion molecules in the basilar artery were measured by RT-PCR. Immunohistochemical study was performed to assess the expression and localization of CD4、CD68and myeloperoxidase (MPO).
Results:SAH could induce increases of the gene expression levels of IL-1β、TNF-α、ICAM-1and VCAM-1, which were reduced in the SAH+SB203580 group.Immunohistochemical study demonstrated that the expression levels of CD4、 CD68and and MPO were all increased in the SAH group, but these increases were attenuated in the SAH+SB203580group.
Conclusion:Inflammatory recaction was evoked by SAH,maybe due to the activation of p38MAPK pathway,and could be suppressed by p38MAPK inhibitor SB203580.
PART HI:Potential role of p38MAPK pathway in the endothelial apoptosis after experimental subarachnoid hemorrhage
Objective:Previous study have demonstrated that p38mitogen-activated protein kinase(MAPK) plays an important role in apoptosis, which is involved in the development of cerebral vasospasm after SAH. This study was conducted to examine whether SB203580,a selective p38MAPK inhibitor could reduce cerebral vasospasm through the suppression of apoptosis.
Methods:48rabbits were assigned randomly to four groups:control, SAH, SAH+DMSO,SAH+SB203580,and were killed on day7. The the endothelial apoptosis was examined by was examined by Western blot analysis of caspase-3activity and TUNEL staining.
Results:Elevated expression of cleaved caspase-3was detected in the basilar artery after SAH and suppresed after SB203580administration. Apoptosis was not detected in the control group. Strong positive cells were visualized in the SAH and SAH+DMSO groups. Weak positive cells were observed in the SAH+SB203580group.
Conclusion:Endothelial apoptosis was evoked by SAH,maybe due to the activation of p38MAPK pathway,and could be suppressed by p38MAPK inhibitor SB203580.
第一部分p38MAPK信号转导通路在蛛网膜下腔出血后脑血管痉挛中的作用
目的：细胞内信号转导通路是近年蛛网膜下腔出血后脑血管痉挛发病机制中的研究热点。p38MAPK信号通路广泛参与组织细胞的生长、存活、分化、凋亡及炎症反应等病理生理过程。本实验旨在研究实验性SAH后p38MAPK在血管壁组织中的表达及其时相,以及应用p38MAPK抑制剂SB203580后脑血管痉挛是否得到改善。
方法：第一组实验中,48例成年新西兰兔,随机分为4组：对照组(n=6),SAH3天组(n=6),SAH5天组(n=6),SAH7天组(n=6)。采用SAH模型为枕大池二次注血模型。分别于第一次注血后第3、5、7天,处死SAH组动物,取基底动脉标本。第二组实验中,24例成年新西兰兔,随机分为4组：对照组(n=6),SAH组(n=6),SAH+DMSO组(n=6),SAH+SB203580组(n=6)。动物模型同第一组实验,于第7天处死所有动物,获得基底动脉标本。Western Blot法测定血管壁组织中总p38MAPK、磷酸化p38MAPK (p-p38MAPK)、总ATF2及磷酸化ATF2的水平。活体灌注后HE染色测量基底动脉管腔面积。
结果：(1)SAH后兔基底动脉p-p38MAPK与P-ATF2的水平在SAH后第3天即有明显升高,第5天达到高峰,第7天略有回落；(2) SB203580可明显降低SAH后p38MAPK、ATF2磷酸化水平,抑制了p38MAPK通路的活性；(3)SB203580明显缓解了脑血管痉挛。
结论：p38MAPK的活性在SAH后痉挛血管中明显上调,其介导的信号通路在SAH后脑血管痉挛的病理过程中起重要作用。
第二部分p38MAPK信号转导通路对蛛网膜下腔出血后脑血管壁炎症反应的作用
目的：血管壁的炎症反应是导致蛛网膜下腔出血后脑血管痉挛的发生以及维持的重要因素。p38MAPK信号通路是参与调控组织细胞炎症反应的重要通路。本实验旨在研究应用p38MAPK特异性抑制齐(?)SB203580对实验性SAH后基底动脉血管壁组织炎症反应的抑制作用。
方法：48例成年新西兰兔,随机分为4组：对照组(n=6),SAH组(n=6),SAH+DMSO组(n=6),SAH+SB203580组(n=6)。动物模型同第一组实验,于第一次注血后第7天,处死所有动物,获得基底动脉标本。RT-PCR法测定血管壁组织中炎性细胞因子IL-1β、TNF-α、ICAM-1、VCAM-1的转录活性,免疫组化法观察血管壁组织中炎症细胞相关抗原CD4、CD68、MPO的表达。
结果：SAH后第7天兔基底动脉组织中炎性细胞因子IL-1β、TNF-α、ICAM-1、 VCAM-1的转录活性均明显增高,炎症细胞相关抗原CD4、CD68、MPO的表达增多。SB203580可明显降低SAH后血管壁组织炎性细胞因子的转录活性和炎症细胞相关抗原的表达。
结论：SAH后血管壁组织存在明显的炎症反应,可能与p38MAPK信号通路的活化有关,应用p38MAPK特异性抑制剂SB203580可明显抑制血管壁炎症反应水平。
第三部分p38MAPK信号转导通路与蛛网膜下腔出血后的脑血管内皮细胞凋亡
目的：血管内皮细胞凋亡是蛛网膜下腔出血后脑血管痉挛发病机制中的重要环节。p38MAPK信号通路是调控组织细胞凋亡的重要通路。本实验旨在研究应用p38MAPK特异性抑制剂SB203580对实验性SAH后基底动脉血管内皮细胞凋亡的抑制作用。
方法：48只成年新西兰兔,随机分为4组：对照组(n=6),SAH组(n=6),SAH+DMSO组(n=6),SAH+SB203580组(n=6)。动物模型同第一组实验,于第一次注血后第7天,处死所有动物,获得基底动脉标本。Western-blot法测定血管壁组织中半胱氨酸蛋白酶-3(caspase-3)的表达,TUNEL法观察血管内皮细胞凋亡情况。
结果：SAH后第7天兔基底动脉组织中;aspase-3的表达明显增高,TUNEL法染色血管内皮细胞阳性染色明显增多。SB203580可明显降低SAH后血管壁组织中caspase-3的活性并抑制血管内皮细胞的凋亡。
结论：SAH后血管内皮细胞存在明显的凋亡,可能与p38MAPK信号通路的活化有关,应用p38MAPK特异性抑制剂SB203580可明显抑制SAH后血管内皮细胞的凋亡。
PART Ⅰ:Potential role of p38MAPK pathway in cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits
Objective:Previous studies have demonstrated signal transduction pathways play a critical role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage and p38MAPK pathway has been shown to be involved in numerous physiological processes, such as cell proliferation,cell survival, apoptosis, inflammation, and embryonic development. This work was conducted to investigate the role of p38MAPK on cerebral vasospasm in a rabbit model of SAH.
Methods:In experiment1,24rabbits were assigned randomly to four groups:control, SAH day3, SAH day5, and SAH day7groups,and were killed on days3,5, and7. The time course of the total p38MAPK,p-p38MAPK,total ATF2and p-ATF2activation in the basilar artery after SAH was analyzed by Wester blot.In experiment2,24rabbits were assigned randomly to four groups:control, SAH, SAH+DMSO,SAH+SB203580,and were killed on day7. The blood vessel cross-sectional area was measured by hematoxylin-eosin staining.
Results:As a result, the elevated expression of activated p-p38MAPK and p-ATF2was detected in the basilar artery after SAH from day3,peaked on day5. After SB203580intracisternal administration, the level of p-p38MAPK and p-ATF2were decreased and the vasospasm was markedly attenuated in the basilar arteries.
Conclusion:p38MAPK pathway was activated in the arterial wall after SAH and contribute to vasospasm development. Administration of p38MAPK inhibitor may attenuate cerebral vasospasm in a rabbit model of SAH.
PART Ⅱ:Potential role of p38MAPK pathway in the inflammatory reaction after experimental subarachnoid hemorrhage
Objective:Inflammatory recaction is involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was conducted to examine whether SB203580,a p38MAPK inhibitor,would suppress inflammatory recaction after experimental SAH.
Methods:48rabbits were assigned randomly to four groups:control, SAH, SAH+DMSO,SAH+SB203580,and were killed on day7. The gene expression levels of cytokines and adhesion molecules in the basilar artery were measured by RT-PCR. Immunohistochemical study was performed to assess the expression and localization of CD4、CD68and myeloperoxidase (MPO).
Results:SAH could induce increases of the gene expression levels of IL-1β、TNF-α、ICAM-1and VCAM-1, which were reduced in the SAH+SB203580 group.Immunohistochemical study demonstrated that the expression levels of CD4、 CD68and and MPO were all increased in the SAH group, but these increases were attenuated in the SAH+SB203580group.
Conclusion:Inflammatory recaction was evoked by SAH,maybe due to the activation of p38MAPK pathway,and could be suppressed by p38MAPK inhibitor SB203580.
PART HI:Potential role of p38MAPK pathway in the endothelial apoptosis after experimental subarachnoid hemorrhage
Objective:Previous study have demonstrated that p38mitogen-activated protein kinase(MAPK) plays an important role in apoptosis, which is involved in the development of cerebral vasospasm after SAH. This study was conducted to examine whether SB203580,a selective p38MAPK inhibitor could reduce cerebral vasospasm through the suppression of apoptosis.
Methods:48rabbits were assigned randomly to four groups:control, SAH, SAH+DMSO,SAH+SB203580,and were killed on day7. The the endothelial apoptosis was examined by was examined by Western blot analysis of caspase-3activity and TUNEL staining.
Results:Elevated expression of cleaved caspase-3was detected in the basilar artery after SAH and suppresed after SB203580administration. Apoptosis was not detected in the control group. Strong positive cells were visualized in the SAH and SAH+DMSO groups. Weak positive cells were observed in the SAH+SB203580group.
Conclusion:Endothelial apoptosis was evoked by SAH,maybe due to the activation of p38MAPK pathway,and could be suppressed by p38MAPK inhibitor SB203580.
引文
[1]Kosty T. Cerebral vasospasm after subarachnoid hemorrhage [J].An update.CritCareNursQ,2005;28(2):122-134.
[2]Dietrich HH and Dacey RG Jr.Molecular keys to the problems of cerebral vasospasm.Neurosurgery.2000;46(3):517-530.
[3]R H Wilkins. Cerebral vasospasm. Crit. Rev. Neurobiol.1990;6:51-77.
[4]Zarubin T, Han JH. Activation and signaling of the p38 MAP kinase pathway.Cell Research.2005;15:11-18.
[5]Sasaki T,Kasuya H,Onda H,Sasahara A,Goto S,Hori T,Inoue I. Role of p38 mitogen-activated protein kinase on cerebral vasospasm after subarachnoid hemorrhage.Stroke.2004;35:1466-1470.
[6]Raingeaud J, Gupta S, Rogers JS, et al. Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine[J].J BiolChem.1995;270(13):7420-7426.
[7]Thuerauf DJ, Arnold ND, Zechner D, et al. p38 Mi-togen-activated protein kinase mediates the transcriptional induction of the atrial natriuretic factor gene through a serum response element. A potential role for the transcription factor ATF6[J]. J Biol Chem.1998;273(32):20636-20643.
[8]Han J, Jiang Y, Li Z, et al. Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation[J]. Nature.1997;386(6622):296-299.
[9]Waskiewicz AJ,Johnson JC,Penn B,et al. Phosphorylation of the cap-binding protein eukeryotic translation initiation factor 4E by protein kinase Mnkl in vivo[J]. Mol Cell Biol.1999; 19(3):1871-1880.
[10]Dumont AS, Dumont RJ, Chow MM, Lin CL, Calisaneller T,Ley KF, Kassell NF, Lee KS. Cerebral vasospasm after subarachnoid hemorrhage:putative role of inflammation.Neurosurgery.2003;53:123-33.
[11]Guan Z, Buckman SY, Pentland AP, Templeton DJ, Morrison AR. Induction of cyclooxygenase-2 by the activated MEKK1→SEK1/MKK4→p38 mitogen-activated protein kinase pathway.J Biol Chem.1998;273:12901-8.
[12]Badger AM,Cook MN,Lark MW,et al.SB 203580 inhibits p38 mitogen-activated protein kinase, nitric oxide production, and inducible nitric oxide synthase in bovine cartilage-derived chondrocytes. J Immunol.1998; 161:467-73.
[13]Da Silva J,Pierrat B,Mary JL,Lesslauer W.Blockade of p38 mitogen-activated protein kinase pathway inhibits inducible nitric-oxide synthase expression in mouse astrocytes. J Biol Chem.1997; 272:28373-80.
[14]Pietersma A, Tilly BC, Gaestel M, et al. p38 mitogen activated protein kinase regulates endothelial VCAM-1 expression at the post-transcriptional level.Biochem Biophys Res Comm.1997;230:44-8.
[15]Lee JC, Laydon JT, McDonnell PC, et al. Identification and characterization of a novel protein kinase involved in the regulation of inflammatory cytokine biosynthesis.Nature.1994;372:739-46.
[16]Pluta RM, Oldfield EH, Boock RJ. Reversal and prevention of cerebral vasospasm by intracarotid infusions of nitric oxide donors in a primate model of subarachnoid hemorrhage. J Neurosurg.1997;87:746-51.
[17]Bombeli T, Karsan A, Tait JF, Harlan JM. Apoptotic vascular endothelial cells become procoagulant.Blood.1997;89:2429-42.
[18]Clower BR, Yamamoto Y, Cain L, Haines DE, Smith RR. Endothelial injury following experimental subarachnoid hemorrhage in rats:effects on brain blood flow.Anat Rec.1994;240:104-14.
[19]Borel CO, McKee A, Parra A, Haglund MM, Solan A, Prabhakar V,Sheng H,Warner DS,Niklason L. Possible role for vascular cell proliferation in cerebral vasospasm after subarachnoid hemorrhage.Stroke.2003;34:427-33.
[1]A.Y. Zubkov, R.E. Tibbs, K. Aoki, J.H. Zhang, Prevention of vasospasm in penetrating arteries with MAPK inhibitors in dog double-hemorrhage model, Surg. Neurol.54 (2000) 221-228.
[2]A. Pasqualin, Epidemiology and pathophysiology of cerebral vasospasm following subarachnoid hemorrhage, J. Neurosurg. Sci.42 (1998) 15-21.
[3]A.Y. Zubkov, A.I. Lewis, F.A. Raila, J. Zhang, A.D. Parent,Risk factors for the development of post-traumatic cerebral vasospasm, Surg. Neurol.53 (2000) 126-130.
[4]P.D. LeRoux, M.M. Haglund, M.R. Mayberg, H.R. Winn,Symptomatic cerebral vasospasm following tumor resection:report of two cases, Surg. Neurol.36 (1991) 25-31.
[5]S. Ries, U. Schminke, K. Fassbender, M. Daffertshofer, W.Steinke, M. Hennerici, Cerebrovascular involvement in the acute phase of bacterial meningitis, J. Neurol.244 (1997)51-55.
[6]N.W. Dorsch, Cerebral arterial spasm*/a clinical review, Br. J.Neurosurg.9 (1995) 403-412.
[7]A.D. Ecker, Does chronic cerebral vasospasm precede development and rupture of intracranial aneurysms? Mayo. Clin. Proc.59 (1984) 797.
[8]R.H. Wilkins, Cerebral vasospasm, Crit. Rev. Neurobiol.6(1990) 51-77.
[9]R.L. Macdonald, B.K. Weir, T.D. Runzer, M.G. Grace, J.M.Findlay, K. Saito, D.A. Cook, B.W. Mielke, K. Kanamaru,Etiology of cerebral vasospasm in primates, J. Neurosurg.75(1991) 415-424.
[10]M. Zuccarello, A.I. Lewis, S. Upputuri, J.B. Farmer, D.K.Anderson, Effect of remacemide hydrochloride on subarachnoid hemorrhage-induced vasospasm in rabbits, J. Neurotrauma.11(1994) 691-698.
[11]H. Zhang, B.K. Weir, R.L. Macdonald, L.S. Marton, N.J.Solenski, A.L. Kwan, K.S. Lee, Mechanisms of Ca2+ ielevation induced by erythrocyte components in endothelial cells, J. Pharmacol. Exp. Ther.277 (1996) 1501-1509.
[12]R.G. Hempelmann, R.H. Pradel, H.L. Barth, H.M. Mehdorn,A. Ziegler, Interactions between vasoconstrictors in isolated human cerebral arteries, Acta Neurochir. (Wien.) 139(1997)574-581.
[13]H. Masaoka, R. Suzuki, Y. Hirata, T. Emori, F. Marumo, K.Hirakawa, Raised plasma endothelin in aneurysmal subarachnoid haemorrhage, Lancet 2 (1989) 1402.
[14]H. Suzuki, S. Sato, Y. Suzuki, M. Oka, T. Tsuchiya, I. Iino, T.Yamanaka, N. Ishihara, S. Shimoda, Endothelin immunoreactivity in cerebrospinal fluid of patients with subarachnoid haemorrhage, Ann. Med.22 (1990) 233-236.
[15]T. Mima, M. Yanagisawa, T. Shigeno, A. Saito, K. Goto, K.Takakura, T. Masaki, Endothelin acts in feline and canine cerebral arteries from the adventitial side, Stroke 20(1989)1553-1556.
[16]K. Ide, K. Yamakawa, T. Nakagomi, T. Sasaki, I. Saito, H.Kurihara, M. Yosizumi, Y. Yazaki, K. Takakura, The role of endothelin in the pathogenesis of vasospasm following subarachnoid haemorrhage, Neurol. Res.11 (1989) 101-104.
[17]T. Asano, I. Ikegaki, Y. Suzuki, S. Satoh, M. Shibuya,Endothelin and the production of cerebral vasospasm in dogs,Biochem. Biophys. Res. Commun.159 (1989) 1345-1351.
[18]J.A. Alabadi, J.B. Salom, G. Torregrosa, F.J. Miranda, T. Jover,E. Alborch, Changes in the cerebrovascular effects of endothelin-1 and nicardipine after experimental subarachnoid hemorrhage,Neurosurgery 33 (1993) 707-714.
[19]S. Roux, B.M. Loffler, G.A. Gray, U. Sprecher, M. Clozel, J.P.Clozel, The role of endothelin in experimental cerebral vasospasm, Neurosurgery 37 (1995) 78-85.
[20]S. Roux, B.M. Loffler, G.A. Gray, U. Sprecher, M. Clozel, J.P.Clozel, The role of endothelin in experimental cerebral vasospasm,Neurosurgery 37 (1995) 78-85.
[21]M. Zuccarello, G.B. Soattin, A.I. Lewis, V. Breu, H. Hallak,R.M. Rapoport, Prevention of subarachnoid hemorrhage-induced cerebral vasospasm by oral administration of endothelin receptor antagonists, J. Neurosurg.84 (1996) 503-507.
[22]A. Hino, B.K. Weir, R.L. Macdonald, R.A. Thisted, C.J. Kim,L.M. Johns, Prospective, randomized, double-blind trial of BQ-123 and bosentan for prevention of vasospasm following subarachnoid hemorrhage in monkeys, J. Neurosurg.83 (1995)503-509.
[23]A.J. Gaw, R.M. Wadsworth, P.P. Humphrey, Neurotransmission in the sheep middle cerebral artery:modulation of responses by 5-HT and haemolysate, J. Cereb. Blood Flow Metab.10(1990) 409-416.
[24]N.A. Svendgaard, L. Edvinsson, C. Owman, C. Sahlin, Increased sensitivity of the basilar artery to norepinephrine and 5-hydroxytryptamine following experimental subarachnoid hemorrhage,Surg. Neurol.8 (1977) 191-195.
[25]A.Y. Zubkov, K. Ogihara, P. Tumu, G.D. Mandybur, A.I.Lewis, A.D. Parent, J.H. Zhang, Bloody cerebospinal fluid alters contraction of cultured arteries, Neurol. Res. 21 (1999) 553-558.
[26]P. Gaetani, C. Cafe, R. Baena, F. Tancioni, C. Torri, F. Tartara,F. Marzatico, Superoxide dismutase activity in cisternal cerebrospinal fluid after aneurysmal subarachnoid haemorrhage,Acta Neurochir. (Wien.) 139(1997) 1033-1037.
[27]K. Iwasa, D.H. Bernanke, R.R. Smith, Y. Yamamoto, Nonmuscle arterial constriction after subarachnoid hemorrhage:role of growth factors derived from platelets, Neurosurgery 32 (1993)619-624.
[28]C.D. Benham, P. Hess, R.W. Tsien, Two types of calcium channels in single smooth muscle cells from rabbit ear artery studied with whole-cell and single-channel recordings, Circ. Res.61 (1987) 110-116.
[29]T.B. Bolton, Mechanisms of action of transmitters and other substances on smooth muscle, Physiol. Rev.59 (1979) 606-718.
[30]C. van Breemen, P. Aaronson, Loutzenhiser, Sodium-calcium interactions in mammalian smooth muscle, Pharmacol. Rev.30(1978) 167-208.
[31]H. Liu, N. Sperelakis, Tyrosine kinases modulate the activity of single L-type calcium channels in vascular smooth muscle cells from rat portal vein, Can. J. Physiol. Pharmacol.75 (1997)1063-1068.
[32]H. Zhang, B. Weir, L.S. Marton, R.L. Macdonald, V. Bindokas,R.J. Miller, J.R. Brorson, Mechanisms of hemolysate-induced [Ca2+]i elevation in cerebral smooth muscle cells, Am. J.Physiol.269 (1995) H1874-H1890.
[33]E. Alborch, J.B. Salom, G. Torregrosa, Calcium channels in cerebral arteries, Pharmacol. Ther.68 (1995) 1-34.
[34]L. Missiaen, H. De Smedt, G. Droogmans, B. Himpens,Casteels, Calcium ion homeostasis in smooth muscle, Pharmacol.Ther.56 (1992) 191-231.
[35]B. Sima, B.K. Weir, R.L. Macdonald, H. Zhang, Extracellular nucleotide-induced [Ca2+]i elevation in rat basilar smooth muscle cells, Stroke 28 (1997) 2053-2058.
[36]S. Iwabuchi, L.S. Marton, J.H. Zhang, Role of protein tyrosine phosphorylation in erythrocyte lysate-induced intracellular free calcium concentration elevation in cerebral smooth-muscle cells,J. Neurosurg.90 (1999) 743-751.
[37]K. Aoki, A.Y. Zubkov, A.D. Parent, J.H. Zhang, Mechanism of ATP-induced [Ca2+](i) mobilization in rat basilar smooth muscle cells, Stroke 31 (2000) 1377-1384.
[38]P. Kim, Y. Yoshimoto, M. lino, S. Tomio, T. Kirino,Nonomura, Impaired calcium regulation of smooth muscle during chronic vasospasm following subarachnoid hemorrhage,J. Cereb. Blood Flow Metab.16 (1996) 334-341.
[39]N.F. Kassell, T. Sasaki, A.R. Colohan, G. Nazar, Cerebral vasospasm following aneurysmal subarachnoid hemorrhage,Stroke 16 (1985) 562-572.
[40]C.J. Kim, B. Weir, R.L. Macdonald, L.S. Marton, H. Zhang,Hemolysate inhibits L-type Ca2+channels in rat basilar smooth muscle cells, J. Vasc. Res.33 (1996) 258-264.
[41]K. Takenaka, H. Yamada, N. Sakai, T. Ando, Y. Okano, Y. Nozawa, Intracellular Ca2+changes in cultured vascular smooth muscle cells by treatment with various spasmogens,Neurol. Res.13 (1991) 168-172.
[42]C.J. Kim, B.K. Weir, R.L. Macdonald, H. Zhang, Erythrocyte lysate releases Ca2+ from IP3-sensitive stores and activates Ca2+-dependent K- channels in rat basilar smooth muscle cells,Neurol. Res.20 (1998) 23-30.
[43]Y. Takanashi, B.K. Weir, B. Vollrath, H. Kasuya, R.L.Macdonald, D. Cook, Time course of changes in concentration of intracellular free calcium in cultured cerebrovascular smooth muscle cells exposed to oxyhemoglobin, Neurosurgery 30 (1992)346-350.
[44]K. Takenaka, J. Kishino, H. Yamada, N. Sakai, H. Arita, Y.Okano, Y. Nozawa, DNA synthesis and intracellular calcium elevation in porcine cerebral arterial smooth muscle cells by cerebrospinal fluid from patients with subarachnoid haemorrhage,Neurol. Res.14 (1992) 330-334.
[45]C. Krueger, B. Weir, M. Nosko, D. Cook, S. Norris, Nimodipine and chronic vasospasm in monkeys:Part 2. Pharmacological studies of vessels in spasm, Neurosurgery 16 (1985) 137-140.
[46]K. Kohno, S. Sakaki, S. Ohue, Y. Kumon, K. Matsuoka,Intracellular calcium levels in canine basilar artery smooth muscle following experimental subarachnoid hemorrhage:an electron microscopic cytochemical study, Acta Neuropathol.(Berl) 81 (1991) 664-669.
[47]W.E. Bulter, J.W. Peterson, N.T. Zervas, K.G. Morgan,Intracellular calcium, myosin light chain phosphorylation, and contractile force in experimental cerebral vasospasm, Neurosurgery 38 (1996) 781-787.
[48]Y. Tanaka, T. Masuzawa, M. Saito, T. Yamada, K. Fujimoto,Change in Ca2+ sensitivity of cerebrovascular smooth muscle in experimental chronic cerebral vasospasm, Neurol. Med. Chir.(Tokyo) 38 (1998) 459-463.
[49]J.T. Stull, P.J. Lin, J.K. Krueger, J. Trewhella, G. Zhi, Myosin light chain kinase: functional domains and structural motifs,Acta Physiol. Scand.164 (1998) 471-482.
[50]A.P. Somlyo, J.W. Walker, Y.E. Goldman, D.R. Trentham, T.Kobayashi, Kitazawa, A.V. Somlyo, Inositol trisphosphate,calcium and muscle contraction, Philos. Trans. R. Soc. Lond.B Biol. Sci.320 (1988) 399-414.
[51]P.F. Dillon, M.O. Aksoy, S.P. Driska, R.A. Murphy, Myosin phosphorylation and the cross-bridge cycle in arterial smooth muscle, Science 211 (1981) 495-497.
[52]I. Kim, B.D. Leinweber, M. Morgalla, W.E. Butler, M. Seto, Y.Sasaki, J.W. Peterson, K.G. Morgan, Thin and thick filament regulation of contractility in experimental cerebral vasospasm,Neurosurgery 46 (2000) 440-446.
[53]T. Harada, M. Seto, Y. Sasaki, S. London, Z. Luo, M. Mayberg,The time course of myosin light-chain phosphorylation in bloodinduced vasospasm, Neurosurgery 36 (1995)1178-1182.
[54]Y. Suzuki, M. Shibuya, M. Takayasu, T. Asano, I. Ikegaki, S.Satoh, M. Saito, H. Hidaka, Protein kinase activity in canine basilar arteries after subarachnoid hemorrhage, Neurosurgery 22(1988) 1028-1031.
[55]M.J. Berridge, Inositol trisphosphate and calcium signalling,Nature 361 (1993) 315-325.
[56]J.W. Walker, A.V. Somlyo, Y.E. Goldman, A.P. Somlyo, D.R.Trentham, Kinetics of smooth and skeletal muscle activation bylaser pulse photolysis of caged inositol 1,4,5-trisphosphate,Nature 327 (1987) 249-252.
[57]B. Vollrath, B.K. Weir, D.A. Cook, Hemoglobin causes release of inositol trisphosphate from vascular smooth muscle, Biochem.Biophys. Res. Commmun.171 (1990)506-511.
[58]B.A. Vollrath, B.K. Weir, R.L. Macdonald, D.A. Cook,Intracellular mechanisms involved in the responses of cerebrovascular smooth-muscle cells to hemoglobin, J. Neurosurg.80(1994) 261-268.
[59]B. Sima, L. MacDonald, L.S. Marton, B. Weir, J. Zhang, Effect of P2-purinoceptor antagonists on hemolysate-induced and adenosine 5?-triphosphate-induced contractions of dog basilar artery in vitro, Neurosurgery 39 (1996)815-821.
[60]Y. Nishizuka, Membrane phospholipid degradation and protein kinase C for cell signalling, Neurosci. Res.15 (1992) 3-5.
[61]K.P. Huang, The mechanism of protein kinase C activation,Trends Neurosci.12 (1989) 425-432.
[62]T. Matsui, Y. Takuwa, H. Johshita, K. Yamashita, T. Asano,Possible role of protein kinase C-dependent smooth muscle contraction in the pathogenesis of chronic cerebral vasospasm, J.Cereb. Blood Flow Metab.11 (1991) 143-149.
[63]W.H. Moolenaar, W. Kruijer, B.C. Tilly, I. Verlaan, A.J.Bierman, S.W. de Laat, Growth factor-like action of phosphatidic acid, Nature 323 (1986) 171-173.
[64]C.L. Yu, M.H. Tsai, D.W. Stacey, Cellular ras activity and phospholipid metabolism, Cell 52 (1988) 63-71.
[65]C.F. Huang, M.C. Cabot, Phorbol diesters stimulate the accumulation of phosphatidate, phosphatidylethanol, and diacylglycerol in three cell types. Evidence for the indirect formation of phosphatidylcholine-derived diacylglycerol by a phospholipase D pathway and direct formation of diacylglycerol by a phospholipase C pathway, J. Biol. Chem.265 (1990) 14858-14863.
[66]E.F. LaBelle, R.M. Fulbright, R.J. Barsotti, H. Gu, E. Polyak,Phospholipase D is activated by G protein and not by calcium ions in vascular smooth muscle, Am. J. Physiol.270 (1996)H1031-H1037.
[67]D.T. Ward, J. Ohanian, A.M. Heagerty, V. Ohanian, Phospholipase D-induced phosphatidate production in intact small arteries during noradrenaline stimulation: involvement of both G-protein and tyrosine-phosphorylation-linked pathways, Biochem.J.307 (1995) 451-456.
[68]A.W. Jones, S.D. Shukla, B.B. Geisbuhler, Stimulation of phospholipase D activity and phosphatidic acid production by norepinephrine in rat aorta, Am. J. Physiol.264 (1993) C609-C616.
[69]J.H. Exton, Signaling through phosphatidylcholine breakdown,J. Biol. Chem.265 (1990) 1-4.
[70]M.M. Billah, J.C. Anthes, The regulation and cellular functions of phosphatidylcholine hydrolysis, Biochem. J.269 (1990) 281-291.
[71]E.J. Freeman, G.M. Chisolm, E.A. Tallant, Role of calcium and protein kinase C in the activation of phospholipase D by angiotensin Ⅱ in vascular smooth muscle cells, Arch. Biochem. Biophys.319 (1995) 84-92.
[72]D.A. Cook, B. Vollrath, Free radicals and intracellular events associated with cerebrovascular spasm, Cardiovasc. Res.30(1995) 493-500.
[73]T. Matsui, Y. Takuwa, H. Kaizu, T. Asano, Possible involvement of C-kinase in occurrence of chronic cerebral vasospasm after subarachnoid hemorrhage, Adv. Exp. Med. Biol.331(1993) 177-182.
[74]Sato M, Tani E, Fujikawa H, Kaibuchi K. Involvement of Rhokinase-mediated phosphorylation of myosin light chain in enhancement of cerebral vasospasm. Circ Res.2000;87:195-200.
[75]Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T,Tamakawa H, Yamagami K, Inui J, Maekawa M, et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. 1997;389:990-994.26.
[76]Chrissobolis S, Sobey CG. Evidence that Rho-kinase activity contributes to cerebral vascular tone in vivo and is enhanced during chronic hypertension comparison with protein kinase C. Circ Res.2001;88:774-779.
[77]Madaule P, Axel R. A novel ras2related gene family. Cell,1985,41:31-40.
[78]Kaibuchi K, Kuroda S, Amano M. Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells.Annu Rev Biochem,1999, 68:459-486.
[79]Riento K, RidleyAJ. Rocks:multifunctional kinases in cell behav2 iour. Nat RevMol Cell Biol,2003,4:446-456.
[80]Matsui T, AmanoM, Yamamoto T, et al. Rho2associated kinase, a novel serine/ threonine kinase, as a putative target for small GTP binding p rotein Rho. EMBO J, 1996,15:2208-2216.
[81]Tosaka M,Okajima F,Hashiba Y, et al. Sphingosine 12phosphate contracts canine basilar arteries in vitro and in vivo:possible role in pathogenesis of cerebral vasospasm [J].Stroke,2001,32 (12):2913-2919.
[82]Wickman G,Lan C,Vollrath B. Functional roles of the RhoP Rho kinase pathway and protein kinase C in the regulation of cerebrovascular constriction mediated by hemoglobin, relevance to subarachnoid hemorrhage and vasospasm[J]. Circ Res,2003,92:809-816.
[83]Lan C,Das D,Wloskowicz A, et al. Endothelin21 modulates hemoglobin2mediated signaling in cerebrovascular smooth muscle via RhoAPRho kinase and protein kinase C [J]. Am J Physiol Heart Circ Physiol,2004,286 (1):H165-173.
[84]Nakamura K, Nishimura J, Hirano K, et al. Hydroxyfasudil, an active metabolite of fasudil hydrochloride, relaxes the rabbit basilar artery by disinhibition of myosin light chain phosphatase. J CerebBlood FlowMetab,2001,21:876-885.
[85]G. Whitney, D. Throckmorton, C. Isales, Y. Takuwa, J. Yeh, H.Rasmussen, C. Brophy, Kinase activation and smooth muscle contraction in the presence and absence of calcium, J. Vasc.Surg.22 (1995) 37-44.
[86]M. Ikebe, D.J. Hartshorne, M. Elzinga, Phosphorylation of the 20 000-dalton light chain of smooth muscle myosin by the calcium-activated, phospholipid-dependent protein kinase. Phosphorylation sites and effects of phosphorylation, J. Biol. Chem. 262 (1987) 9569-9573.
[87]T. Matsui, M. Sugawa, H. Johshita, Y. Takuwa, T. Asano,Activation of the protein kinase C-mediated contractile system in canine basilar artery undergoing chronic vasospasm, Stroke 22(1991) 1183-1187.
[88]S. Nishizawa, N. Nezu, K. Uemura, Direct evidence for a key role of protein kinase C in the development of vasospasm after subarachnoid hemorrhage, J. Neurosurg.76 (1992) 635-639..
[89]S. Nishizawa, J.W. Peterson, I. Shimoyama, K. Uemura,Relation between protein kinase C and calmodulin systems in cerebrovascular contraction:investigation of the pathogenesis of vasospasm after subarachnoid hemorrhage, Neurosurgery 31(1992) 711-716.
[90]M. Sako, J. Nishihara, S. Ohta, J. Wang, S. Sakaki, Role of protein kinase C in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage, J. Cereb. Blood Flow Metab.13(1993)247-254.
[91]Y. Takuwa, T. Matsui, Y. Abe, T. Nagafuji, K. Yamashita, T.Asano, Alterations in protein kinase C activity and membrane lipid metabolism in cerebral vasospasm after subarachnoid hemorrhage, J. Cereb. Blood Flow Metab.13 (1993) 409-415.
[92]M. Zuccarello, C.L. Bonasso, A.I. Lewis, N. Sperelakis, R.M.Rapoport, Relaxation of subarachnoid hemorrhage-induced spasm of rabbit basilar artery by the K+-channel activator cromakalim, Stroke 27 (1996) 311-316.
[93]E. Tachibana, T. Harada, M. Shibuya, K. Saito, M. Takayasu,Y. Suzuki, J. Yoshida, Intra-arterial infusion of fasudil hydrochloride for treating vasospasm following subarachnoid haemorrhage,Acta Neurochir. (Wien.) 141 (1999) 13-19.
[94]M.D. Hollenberg, Tyrosine kinase pathways and the regulation of smooth muscle contractility, Trends Pharmacol. Sci.15 (1994)108-114.
[95]N. Kaplan, J. Di Salvo, Coupling between [arginine8]-vasopressin-activated increases in protein tyrosine phosphorylation and cellular calcium in A7r5 aortic smooth muscle cells, Arch.Biochem. Biophys.326 (1996) 271-280.
[96]T. Gokita, Y. Miyauchi, M.K. Uchida, Effects of tyrosine kinase inhibitor, genistein, and phosphotyrosine-phosphatase inhibitor,orthovanadate, on Ca2+-free contraction of uterine smooth muscle of the rat, Gen. Pharmacol.25 (1994) 1673-1677.
[97]W. Abebe, D.K. Agrawal, Role of tyrosine kinases in norepinephrine-induced contraction of vascular smooth muscle, J.Cardiovasc. Pharmacol.26 (1995) 153-159.
[98]S. Lev, H. Moreno, R. Martinez, P. Canoll, E. Peles, J.M. Musacchio, G.D. Plowman, B. Rudy, J. Schlessinger, Protein tyrosine kinase PYK2 involved in Ca2+-induced regulation of ion channel and MAP kinase functions, Nature 376 (1995) 737-745.
[99]S.A. Siegelbaum, Channel regulation. Ion channel control by tyrosine phosphorylation, Curr. Biol.4 (1994) 242-245.
[100]M. Watanabe, M. Doi, K. Sasaki, A. Ogawa, Modulatory role of protein tyrosine kinase activation in the receptor-induced contractions of the bovine cerebral artery, Neurol. Med. Chir.(Tokyo) 38 (1998) 75-81.
[101]A.Y. Zubkov, K.S. Rollins, A.D. Parent, J. Zhang, R.M. Bryan,Mechanism of endothelin-1-induced contraction in rabbit basilar artery, Stroke 31 (2000) 526-533.
[102]L.S. Marton, B.K. Weir, H. Zhang, Tyrosine phosphorylation and [Ca2+]i elevation induced by hemolysate in bovine endothelial cells:implications for cerebral vasospasm, Neurol. Res.18 (1996) 349-353.
[103]C.J. Kim, B.K. Weir, R.L. Macdonald, H. Zhang, Erythrocyte lysate releases Ca2+from IP3-sensitive stores and activates Ca2+-dependent K+ channels in rat basilar smooth muscle cells, Neurol. Res.20 (1998) 23-30.
[104]B. Vollrath, D. Cook, J. Megyesi, J.M. Findlay, H. Ohkuma,Novel mechanism by which hemoglobin induces constriction of cerebral arteries, Eur. J. Pharmacol.361 (1998)311-319.
[105]T.J. Childs, A.S. Mak, MAP kinases from bovine brain:purification and characterization, Biochem. Cell Biol.71 (1993)544-555.
[106]K.K. Griendling, M. Ushio-Fukai, B. Lassegue, R.W. Alexander,Angiotensin II signaling in vascular smooth muscle. New concepts, Hypertension 29 (1997) 366-373.
[107]M.H. Watson, S.L. Venance, S.C. Pang, A.S. Mak, Smooth muscle cell proliferation. Expression and kinase activities of p34cdc2 and mitogen-activated protein kinase homologues, Circ.Res.73 (1993) 109-117.
[108]H. Sun, N.K. Tonks, D. Bar-Sagi, Inhibition of Ras-induced DNA synthesis by expression of the phosphatase MKP-1,Science 266 (1994) 285-288.
[109]S.S. Katoch, R.S. Moreland, Agonist and membrane depolarization induced activation of MAP kinase in the swine carotid artery, Am. J. Physiol.269 (1995) H222-H229.
[110]A.Y. Zubkov, K. Ogihara, P. Tumu, A. Patlolla, A.I. Lewis,A.D. Parent, J. Zhang, Mitogen-activated protein kinase mediation of hemolysate-induced contraction in rabbit basilar artery,J. Neurosurg.90 (1999) 1091-1097.
[111]H. Fujikawa, E. Tani, I. Yamaura, I. Ozaki, K. Miyaji, M. Sato,K. Takahashi, S. Imajoh-Ohmi, Activation of protein kinases in canine basilar artery in vasospasm, J. Cereb. Blood Flow Metab.19 (1999) 44-52.
[112]P. Rodriguez-Viciana, P.H. Warne, B. Vanhaesebroeck, M.D.Waterfield, J. Downward, Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation, EMBO J.15 (1996) 2442-2451.
[113]J. Suga, Y. Yoshimasa, K. Yamada, Y. Yamamoto, G. Inoue,M. Okamoto, M. Hayashi, Shigemoto, A. Kosaki, H. Kuzuya,K. Nakao, Differential activation of mitogen-activated protein kinase by insulin and epidermal growth factor in 3T3-L1 adipocytes:a possible involvement of PI3-kinase in the activation of the MAP kinase by insulin, Diabetes 46 (1997) 735-741.
[114]K. Osuka, Y. Suzuki, T. Tanazawa, K. Hattori, N. Yamamoto,M. Takayasu, M. Shibuya, J. Yoshida, Interleukin-6 and development of vasospasm after subarachnoid haemorrhage,Acta Neurochir. (Wien.) 140 (1998) 943-951.
[115]I. Guillet-Deniau, A.F. Burnol, J. Girard, Identification and localization of a skeletal muscle secrotonin 5-HT2A receptor coupled to the Jak/STAT pathway, J. Biol. Chem.272 (1997)14825-14829.
[116]D.W. Love, A.J. Whatmore, P.E. Clayton, C.M. Silva, Growth hormone stimulation of the mitogen-activated protein kinase pathway is cell type specific, Endocrinology 139 (1998) 1965-1971.
[117]L.P. Adam, J.R. Haeberle, D.R. Hathaway, Phosphorylation of caldesmon in arterial smooth muscle, J. Biol. Chem.264 (1989)7698-7703.
[118]L.P. Adam, D.R. Hathaway, Identification of mitogen-activated protein kinase phosphorylation sequences in mammalian h-Caldesmon, FEBS Lett.322 (1993) 56-60.
[119]J.J. Earley, X. Su, R.S. Moreland, Caldesmon inhibits active crossbridges in unstimulated vascular smooth muscle:an antisense oligodeoxynucleotide approach, Circ. Res.83 (1998) 661-667.
[120]Z. Wang, H. Jiang, Z.Q. Yang, S. Chacko, Both N-terminal myosin-binding and C-terminal actin-binding sites on smooth muscle caldesmon are required for caldesmon-mediated inhibition of actin filament velocity, Proc. Natl. Acad. Sci. USA 94(1997)11899-11904.
[121]T. Itoh, A. Suzuki, Y. Watanabe, T. Mino, M. Naka, T. Tanaka,A calponin peptide enhances Ca2+ sensitivity of smooth muscle contraction without affecting myosin light chain phosphorylation,J. Biol. Chem.270 (1995) 20400-20403.
[122]M. Doi, H. Kasuya, B. Weir, D.A. Cook, A. Ogawa, Reduced expression of calponin in canine basilar artery after subarachnoid haemorrhage, Acta Neurochir. (Wien.) 139 (1997) 77-81.
[123]C.B. Menice, J. Hulvershorn, L.P. Adam, C.A. Wang, K.G.Morgan, Calponin and mitogen-activated protein kinase signaling in differentiated vascular smooth muscle, J. Biol. Chem.272(1997) 25157-25161.
[124]Z. Xiong, N. Sperelakis, C. Fenoglio-Preiser, Regulation of Ltype calcium channels by cyclic nucleotides and phosphorylation in smooth muscle cells from rabbit portal vein, J. Vasc. Res.31(1994) 271-279.
[125]P. de Lanerolle, M. Nishikawa, D.A. Yost, R.S. Adelstein,Increased phosphorylation of myosin light chain kinase after an increase in cyclic AMP in intact smooth muscle, Science 223(1984) 1415-1417.
[126]R.V. Vegesna, J. Diamond, Effects of isoproterenol and forskolin on tension, cyclic AMP levels, and cyclic AMP dependent protein kinase activity in bovine coronary artery,Can. J. Physiol. Pharmacol.62 (1984) 1116-1123.
[127]H. Todo, S. Ohta, J. Wang, H. Ichikawa, S. Ohue, Y. Kumon, S.Sakaki, Impairment in biochemical level of arterial dilative capability of a cyclic nucleotides-dependent pathway by induced vasospasm in the canine basilar artery, J. Cereb. Blood Flow Metab.18 (1998) 808-817.
[128]D.H. Edwards, J.V. Byrne, T.M. Griffith, The effect of chronic subarachnoid hemorrhage on basal endothelium-derived relaxing factor activity in intrathecal cerebral arteries, J. Neurosurg.76 (1992) 830-837.
[129]R.L. Macdonald, B.K. Weir, A review of hemoglobin and the pathogenesis of cerebral vasospasm, Stroke 22 (1991) 971-982.
[130]C.G. Sobey, F.M. Faraci, Effects of a novel inhibitor of guanylyl cyclase on dilator responses of mouse cerebral arterioles, Stroke28 (1997) 837-842.
[131]P. Kim, V.B. Schini, T.M.J. Sundt, P.M. Vanhoutte, Reduced production of cGMP underlies the loss of endothelium-dependent relaxations in the canine basilar artery after subarachnoid hemorrhage, Circ. Res.70 (1992) 248-256.
[132]H. Kasuya, B.K. Weir, M. Nakane, J.S. Pollock, L. Johns, L.S.Marton, K. Stefansson, Nitric oxide synthase and guanylate cyclase levels in canine basilar artery after subarachnoid hemorrhage, J. Neurosurg.82 (1995) 250-255.
[133]P. Kim, Loss of relaxations, metabolic failure and increased calcium permeability of smooth muscle during chronic cerebral vasospasm, J. Auton. Nerv. Syst.49 (Suppl.) (1994) S157-S162.
[134]C.G. Sobey, F.M. Faraci, Subarachnoid haemorrhage:what happens to the cerebral arteries? Clin. Exp. Pharmacol. Physiol.25 (1998) 867-876.
[135]D.R. Harder, P. Dernbach, A. Waters, Possible cellular mechanism for cerebral vasospasm after experimental subarachnoid hemorrhage in the dog, J. Clin. Invest.80 (1987) 875-880.
[136]R. Tibbs, A. Zubkov, K. Aoki, T. Meguro, A. Badr, A. Parent,J. Zhang, Effects of mitogen-activated protein kinase inhibitors on cerebral vasospasm in a double-hemorrhage model in dogs, J.Neurosurg.93 (2000) 1041-1047.
[137]H. Onda, H. Kasuya, K. Takakura, T. Hori, T. Imaizumi, T.Takeuchi, I. Inoue, J. Takeda, Identification of genes differentially expressed in canine vasospastic cerebral arteries after subarachnoid hemorrhage, J. Cereb. Blood Flow Metab.19(1999) 1279-1288.
[138]Y. Aihara, H. Kasuya, H. Onda, T. Hori, J. Takeda, F.M.Faraci, Quantitative analysis of gene expressions related to inflammation in canine spastic artery after subarachnoid hemorrhage editorial comment, Stroke 32 (2001) 212-217.
1. Brewster, J.L., et al., An osmosensing signal transduction pathway in yeast. Science,1993.259(5102):p.1760-3.
2. Han, J., et al., A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science,1994.265(5173):p.808-11.
3. Hale, K.K., et al., Differential expression and activation of p38 mitogen-activated protein kinase alpha, beta, gamma, and delta in inflammatory cell lineages. Journal of Immunology,1999.162(7):p.4246-52.
4. Rouse, J., et al., A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins. Cell,1994.78(6):p.1027-37.
5. Shapiro, L., et al., Interleukin 18 stimulates HIV type 1 in monocytic cells. Proceedings of the National Academy of Sciences of the United States of America,1998.95(21):p.12550-5.
6. Foltz, I.N., et al., Hemopoietic growth factors with the exception of interleukin-4 activate the p38 mitogen-activated protein kinase pathway. Journal of Biological Chemistry,1997.272(6):p.3296-301.
7. Sweeney, G., et al., An inhibitor of p38 mitogen-activated protein kinase prevents insulin-stimulated glucose transport but not glucose transporter translocation in 3T3-L1 adipocytes and L6 myotubes. Journal of Biological Chemistry,1999.274(15):p.10071-8.
8. Heidenreich, K.A. and J.L. Kummer, Inhibition of p38 mitogen-activated protein kinase by insulin in cultured fetal neurons. Journal of Biological Chemistry,1996.271(17):p.9891-4.
9. Enslen, H., J. Raingeaud, and R.J. Davis, Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6. Journal of Biological Chemistry,1998.273(3):p.1741-8.
10. Jiang, Y., et al., Characterization of the structure and function of the fourth member of p38 group mitogen-activated protein kinases, p38delta. Journal of Biological Chemistry,1997.272(48):p.30122-8.
11. Ge, B., et al., MAPKK-independent activation of p38alpha mediated by TAB1-dependent autophosphorylation of p38alpha. Science,2002.295(5558): p.1291-4.
12. Bagrodia, S., et al., Cdc42 and PAK-mediated signaling leads to Jun kinase and p38 mitogen-activated protein kinase activation. Journal of Biological Chemistry,1995.270(47):p.27995-8.
13. Zhang, S., et al., Rho family GTPases regulate p38 mitogen-activated protein kinase through the downstream mediator Pakl. Journal of Biological Chemistry,1995.270(41):p.23934-6.
14. Nick, J.A., et al., Common and distinct intracellular signaling pathways in human neutrophils utilized by platelet activating factor and FMLP. Journal of Clinical Investigation,1997.99(5):p.975-86.
15. Manser, E., et al., A brain serine/threonine protein kinase activated by Cdc42 and Racl. Nature,1994.367(6458):p.40-6.
16. Jackson, P.F. and J.L. Bullington, Pyridinylimidazole based p38 MAP kinase inhibitors. Curr Top Med Chem,2002.2(9):p.1011-20.
17. Cirillo, P.F., C. Pargellis, and J. Regan, The non-diaryl heterocycle classes of p38 MAP kinase inhibitors. Curr Top Med Chem,2002.2(9):p.1021-35.
18. Lee, J.C., et al., Inhibition of p38 MAP kinase as a therapeutic strategy. Immunopharmacology,2000.47(2-3):p.185-201.
19. Thuerauf, D.J., et al., p38 Mitogen-activated protein kinase mediates the transcriptional induction of the atrial natriuretic factor gene through a serum response element. A potential role for the transcription factor ATF6. Journal of Biological Chemistry,1998.273(32):p.20636-43.
20. Ferrer, I., et al., Early modifications in the expression of mitogen-activated protein kinase (MAPK/ERK), stress-activated kinases SAPK/JNK and p38, and their phosphorylated substrates following focal cerebral ischemia. Acta Neuropathol,2003.105(5):p.425-37.
21. Borsch-Haubold, A.G., R.M. Kramer, and S.P. Watson, Phosphorylation and activation of cytosolic phospholipase A2 by 38-kDa mitogen-activated protein kinase in collagen-stimulated human platelets. European Journal of Biochemistry,1997.245(3):p.751-9.
22. Guan, Z., et al., Induction of cyclooxygenase-2 by the activated MEKKI --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway. Journal of Biological Chemistry,1998.273(21):p.12901-8.
23. Badger, A.M., et al., SB 203580 inhibits p38 mitogen-activated protein kinase, nitric oxide production, and inducible nitric oxide synthase in bovine cartilage-derived chondrocytes. Journal of Immunology,1998.161(1):p. 467-73.
24. Da Silva, J., et al., Blockade of p38 mitogen-activated protein kinase pathway inhibits inducible nitric-oxide synthase expression in mouse astrocytes. Journal of Biological Chemistry,1997.272(45):p.28373-80.
25. Craxton, A., et al., p38 MAPK is required for CD40-induced gene expression and proliferation in B lymphocytes. Journal of Immunology,1998.161(7):p. 3225-36.
26. Pietersma, A., et al., p38 mitogen activated protein kinase regulates endothelial VCAM-1 expression at the post-transcriptional level. Biochemical and Biophysical Research Communications,1997.230(1):p.44-8.
27. Lee, J.C., et al., A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature,1994.372(6508):p.739-46.
28. Xia, Z., et al., Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science,1995.270(5240):p.1326-31.
29. Juo, P., et al., Fas activation of the p38 mitogen-activated protein kinase signalling pathway requires ICE/CED-3 family proteases. Molecular and Cellular Biology,1997.17(1):p.24-35.
30. Huang, S., et al., Apoptosis signaling pathway in T cells is composed of ICE/Ced-3 family proteases and MAP kinase kinase 6b. Immunity,1997.6(6): p.739-49.
31. Cardone, M.H., et al., The regulation of anoikis:MEKK-1 activation requires cleavage by caspases. Cell,1997.90(2):p.315-23.
32. Ziegler-Heitbrock, H.W., et al., In vitro desensitization to lipopolysaccharide suppresses tumour necrosis factor, interleukin-1 and interleukin-6 gene expression in a similar fashion. Immunology,1992.75(2):p.264-8.
33. Koike, N., et al., Effects of adding P38 mitogen-activated protein-kinase inhibitor to celsior solution in canine heart transplantation from non-heart-beating donors. Transplantation,2004.77(2):p.286-92.
34. 王雨,田伏洲,汤礼军,等.p38信号转导途径对离体肝脏缺血再灌注损伤的影响[J].中华肝脏病杂志,2003,11(3)：p.170-2.
35. 王雨,汤礼军,戴睿夫,等.p38 MAPK信号转导途径对缺血再灌注早期离体肝脏细胞因子表达的影响[J].中国普外基础与临床杂志,2009,16(6)：p.443-8.
36. Kim, E.S., M.S. Kim, and A. Moon, TGF-beta-induced upregulation of MMP-2 and MMP-9 depends on p38 MAPK, but not ERK signaling in MCF10A human breast epithelial cells. International Journal of Oncology, 2004.25(5):p.1375-82.
37. Wang, W.H., R.L. Hullinger, and O.M. Andrisani, Hepatitis B virus X protein via the p38MAPK pathway induces E2F1 release and ATR kinase activation mediating p53 apoptosis. Journal of Biological Chemistry,2008.283(37):p. 25455-67.
38. Kim, M.S., et al., p38 kinase is a key signaling molecule for H-Ras-induced cell motility and invasive phenotype in human breast epithelial cells. Cancer Research,2003.63(17):p.5454-61.
39. Ke, Z., et al., MMP-2 mediates ethanol-induced invasion of mammary epithelial cells over-expressing ErbB2. International Journal of Cancer,2006. 119(1):p.8-16.
40. Huang, X., et al., Genistein inhibits p38 map kinase activation, matrix metalloproteinase type 2, and cell invasion in human prostate epithelial cells. Cancer Research,2005.65(8):p.3470-8.
41. Yu, J., et al., p38 Mitogen-activated protein kinase regulation of endothelial cell migration depends on urokinase plasminogen activator expression. Journal of Biological Chemistry,2004.279(48):p.50446-54.
42. Shin, B.A., et al., P38 MAPK pathway is involved in the urokinase plasminogen activator expression in human gastric SNU-638 cells. Oncology Reports,2003.10(5):p.1467-71.
43. Greenberg, A.K., et al., Selective p38 activation in human non-small cell lung cancer. American Journal of Respiratory Cell and Molecular Biology,2002. 26(5):p.558-64.
44. Liao, P., et al., The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy. Proceedings of the National Academy of Sciences of the United States of America,2001.98(21):p.12283-8.
45. Zhang, S., et al., The role of the Grb2-p38 MAPK signaling pathway in cardiac hypertrophy and fibrosis. Journal of Clinical Investigation,2003. 111(6):p.833-41.
46. Gao, F., et al., p38 MAPK inhibition reduces myocardial reperfusion injury via inhibition of endothelial adhesion molecule expression and blockade of PMN accumulation. Cardiovascular Research,2002.53(2):p.414-22.
47. Das, D.K., et al., Reactive oxygen species function as second messenger during ischemic preconditioning of heart. Molecular and Cellular Biochemistry,1999.196(1-2):p.59-67.
48. Stern, M.P., Diabetes and cardiovascular disease. The "common soil" hypothesis. Diabetes,1995.44(4):p.369-74.
49. Ju, H., et al., p38 MAPK inhibitors ameliorate target organ damage in hypertension:Part 1. p38 MAPK-dependent endothelial dysfunction and hypertension. Journal of Pharmacology and Experimental Therapeutics,2003. 307(3):p.932-8.
50. Paris, D., et al., Cholesterol modulates vascular reactivity to endothelin-1 by stimulating a pro-inflammatory pathway. Biochemical and Biophysical Research Communications,2000.274(2):p.553-8.
51. Bokemeyer, D., A. Sorokin, and M.J. Dunn, Multiple intracellular MAP kinase signaling cascades. Kidney International,1996.49(5):p.1187-98.
52. Kyaw, M., et al., Antioxidants inhibit JNK and p38 MAPK activation but not ERK 1/2 activation by angiotensin Ⅱ in rat aortic smooth muscle cells. Hypertension Research,2001.24(3):p.251-61.
53. Sun, A., et al., P38 MAP kinase is activated at early stages in Alzheimer's disease brain. Experimental Neurology,2003.183(2):p.394-405.
54. Otth, C., et al., Modulation of the JNK and p38 pathways by cdk5 protein kinase in a transgenic mouse model of Alzheimer's disease. Neuroreport,2003. 14(18):p.2403-9.
55. 刘华,徐祖才,夏杰,等.p38 MAPK信号通路在癫大鼠海马结构中的激活.重庆医学,2007,36：p.1259-1260.
56. Poolos, N.P., J.B. Bullis, and M.K. Roth, Modulation of h-channels in hippocampal pyramidal neurons by p38 mitogen-activated protein kinase. Journal of Neuroscience,2006.26(30):p.7995-8003.
1. Zhou, C., et al., Caspase inhibitors prevent endothelial apoptosis and cerebral vasospasm in dog model of experimental subarachnoid hemorrhage. Journal of Cerebral Blood Flow and Metabolism,2004.24(4):p.419-31.
2. Dietrich, H.H. and R.G Dacey, Jr., Molecular keys to the problems of cerebral vasospasm. Neurosurgery,2000.46(3):p.517-30.
3. Zubkov, A.Y., A. Nanda, and J.H. Zhang, Signal transduction pathways in cerebral vasospasm. Pathophysiology,2003.9(2):p.47-61.
4. Zhou, M.L., et al., Expression of Toll-like receptor 4 in the basilar artery after experimental subarachnoid hemorrhage in rabbits:a preliminary study. Brain Research,2007.1173:p.110-6.
5. Chen, G, et al., Potential role of JAK2 in cerebral vasospasm after experimental subarachnoid hemorrhage. Brain Research,2008.1214:p. 136-44.
6. Irving, E.A. and M. Bamford, Role of mitogen-and stress-activated kinases in ischemic injury. Journal of Cerebral Blood Flow and Metabolism,2002.22(6): p.631-47.
7. Yamaguchi, M., et al., Ras protein contributes to cerebral vasospasm in a canine double-hemorrhage model. Stroke,2004.35(7):p.1750-5.
8. Varsos, V.G., et al., Delayed cerebral vasospasm is not reversible by aminophylline, nifedipine, or papaverine in a "two-hemorrhage" canine model. Journal of Neurosurgery,1983.58(1):p.11-7.
9. Zhen, X., et al., The p38 mitogen-activated protein kinase is involved in associative learning in rabbits. Journal of Neuroscience,2001.21(15):p. 5513-9.
10. Zhou, M.L., et al., Comparison between one- and two-hemorrhage models of cerebral vasospasm in rabbits. Journal of Neuroscience Methods,2007. 159(2):p.318-24.
11. Zarubin, T. and J. Han, Activation and signaling of the p38 MAP kinase pathway. Cell Research,2005.15(1):p.11-8.
12. Kumar, S., et al., Novel homologues of CSBP/p38 MAP kinase:activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles. Biochemical and Biophysical Research Communications,1997.235(3):p. 533-8.
13. Parker, C.G., et al., Identification of stathmin as a novel substrate for p38 delta. Biochemical and Biophysical Research Communications,1998.249(3):p. 791-6.
14. Jiang, Y., et al., Characterization of the structure and function of the fourth member of p38 group mitogen-activated protein kinases, p38delta. Journal of Biological Chemistry,1997.272(48):p.30122-8.
15. Sun, H., et al., MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo. Cell,1993. 75(3):p.487-93.
1. Treggiari-Venzi, M.M., P.M. Suter, and J.A. Romand, Review of medical prevention of vasospasm after aneurysmal subarachnoid hemorrhage:a problem of neurointensive care. Neurosurgery,2001.48(2):p.249-61; discussion 261-2.
2. Zhou, C., et al., Caspase inhibitors prevent endothelial apoptosis and cerebral vasospasm in dog model of experimental subarachnoid hemorrhage. Journal of Cerebral Blood Flow and Metabolism,2004.24(4):p.419-31.
3. Dietrich, H.H. and R.G. Dacey, Jr., Molecular keys to the problems of cerebral vasospasm. Neurosurgery,2000.46(3):p.517-30.
4. Dumont, A.S., et al., Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation. Neurosurgery,2003.53(1):p.123-33; discussion 133-5.
5. Lee, J.C., et al., A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature,1994.372(6508):p.739-46.
6. Ridley, S.H., et al., Actions of IL-1 are selectively controlled by p38 mitogen-activated protein kinase:regulation of prostaglandin H synthase-2, metalloproteinases, and IL-6 at different levels. Journal of Immunology,1997. 158(7):p.3165-73.
7. Ohashi, N., et al., Role of p38 mitogen-activated protein kinase in neointimal hyperplasia after vascular injury. Arteriosclerosis, Thrombosis, and Vascular Biology,2000.20(12):p.2521-6.
8. Varsos, V.G, et al., Delayed cerebral vasospasm is not reversible by aminophylline, nifedipine, or papaverine in a "two-hemorrhage"canine model. Journal of Neurosurgery,1983.58(1):p.11-7.
9. Zhen, X., et al., The p38 mitogen-activated protein kinase is involved in associative learning in rabbits. Journal of Neuroscience,2001.21(15):p. 5513-9.
10. Bombeli, T., et al., Apoptotic vascular endothelial cells become procoagulant. Blood,1997.89(7):p.2429-42.
11. Guan, Z., et al., Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway. Journal of Biological Chemistry,1998.273(21):p.12901-8.
12. Da Silva, J., et al., Blockade of p38 mitogen-activated protein kinase pathway inhibits inducible nitric-oxide synthase expression in mouse astrocytes. Journal of Biological Chemistry,1997.272(45):p.28373-80.
13. Craxton, A., et al., p38 MAPK is required for CD40-induced gene expression and proliferation in B lymphocytes. Journal of Immunology,1998.161(7):p. 3225-36.
14. Pietersma, A., et al., p38 mitogen activated protein kinase regulates endothelial VCAM-1 expression at the post-transcriptional level. Biochemical and Biophysical Research Communications,1997.230(1):p.44-8.
15. Aihara, Y., et al., Quantitative analysis of gene expressions related to inflammation in canine spastic artery after subarachnoid hemorrhage. Stroke, 2001.32(1):p.212-7.
16. Kubota, T., et al., The kinetics of lymphocyte subsets and macrophages in subarachnoid space after subarachnoid hemorrhage in rats. Stroke,1993. 24(12):p.1993-2000; discussion 2000-1.
17. Sullivan, GW., I.J. Sarembock, and J. Linden, The role of inflammation in vascular diseases. Journal of Leukocyte Biology,2000.67(5):p.591-602.
18. Fassbender, K., et al., Endothelin-1 in subarachnoid hemorrhage:An acute-phase reactant produced by cerebrospinal fluid leukocytes. Stroke,2000. 31(12):p.2971-5.
19. Oshiro, E.M., et al., Inhibition of experimental vasospasm with anti-intercellular adhesion molecule-1 monoclonal antibody in rats. Stroke, 1997.28(10):p.2031-7; discussion 2037-8.
l.Treggiari-Venzi MM, Suter PM, Romand JA.Review of medical prevention of vasospasm after aneurismal subarachnoid hemorrhage:a problem of neurointensive care. Neurosurgery 2001;48:249-261.
2.Cahill J, Calvert JW, Solaroglu I, Zhang JH.Vasospasm and p53-induced apoptosis in an experimental model of subarachnoid hemorrhage. Stroke 2006;37:1868-1874.
3.Zhou C, Yamaguchi M, Kusaka G, Schonholz C, Nanda A, Zhang JH. Caspase inhibitors prevent endothelial apoptosis and cerebral vasospasm in dog model of experimental subarachnoid hemorrhage. J Cereb Blood Flow Metab 2004;24:419-431.
4. Dietrich HH, Dacey Jr RG. Molecular keys to the problems of cerebral vasospasm. Neurosurgery 2000;46:517-30.
5.Varsos VG, Liszczak TM, Han DH, Kistler JP,Vielma J,Black PM,Heros RC,Zervas NT.Delayed cerebral vasospasm is not reversible by aminophylline, nifedipine,or papaverine in a 'two-hemorrhage' canine model. J Neurosurg 1983;58:11-7.
6.Zhen XC,Du W,Romano AG,Friedman E,Harvey JA. The p38 mitogen-activated protein kinase is involved in associative learning in rabbits. J Neuroscience 2001;21:5513-5519.
7.Zhou ML,Shi JX,Zhu JQ,Hang CH,Mao L,Chen KF,Yin HX. Comparison between one- and two-hemorrhage models of cerebral vasospasm in rabbits. J Neurosci Methods 2007; 159:318-324.
8.Chen G, Jiang JY, Shi JX,Ai JL,Hang CH. Effects of recombinant human erythropoietin (rhEPO) on JAK2/STAT3 pathway and endothelial apoptosis in the rabbit basilar artery after subarachnoid hemorrhage. Cytokine 2009;45:162-8.
9.Meguro T, Chen B, Lancon J, Zhang JH. Oxyhemoglobin induces caspase mediated cell death in cerebral endothelial cells. J Neurochem 2001;77:1128-35.
10.Pluta RM, Oldfield EH, Boock RJ. Reversal and prevention of cerebral vasospasm by intracarotid infusions of nitric oxide donors in a primate model of subarachnoid hemorrhage. J Neurosurg 1997;87:746-51.
11.Bombeli T, Karsan A, Tait JF, Harlan JM. Apoptotic vascular endothelial cells become procoagulant. Blood 1997;89:2429-42.
12.Macdonald RL, Weir BK, Runzer TD, Grace MG, Findlay JM, Saito K, Cook DA,Mielke BW,Kanamaru K. Etiology of cerebral vasospasm in primates. J Neurosurg 1991;75:415-24.
13.Clower BR, Yamamoto Y, Cain L, Haines DE, Smith RR. Endothelial injury following experimental subarachnoid hemorrhage in rats:effects on brain blood flow. Anat Rec 1994;240:104-14.
14.Borel CO, McKee A, Parra A, Haglund MM, Solan A, Prabhakar V,Sheng H,Warner DS,Niklason L. Possible role for vascular cell proliferation in cerebral vasospasm after subarachnoid hemorrhage. Stroke 2003;34:427-33.
15.Zarubin T, Han JH. Activation and signaling of the p38 MAP kinase pathway. Cell Research 2005;15:11-18.
16.Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME.Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 1995; 270:1326-31.
17.Juo P, Kuo CJ, Reynolds SE,Konz RF,Raingeaud J,Davis RJ,Biemann HP,Blenis J. Fas activation of the p38 mitogen-activated protein kinase signalling pathway requires ICE/CED-3 family proteases. Mol Cell Biol 1997; 17:24-35.
18.Huang S, Jiang Y, Li Z,Nishida E,Mathias P,Lin S,Ulevitch RJ,Nemerow GR,Han J. Apoptosis signaling pathway in T cells is composed of ICE/Ced-3 family proteases and MAP kinase kinase 6β. Immunity 1997; 6:739-49.
19.Cardone MH, Salvesen GS, Widmann C, Johnson G, Frisch SM.The regulation of anoikis:MEKK-1 activation requires cleavage by caspases. Cell 1997; 90:315-23.
20.Sasaki T,Kasuya H,Onda H,Sasahara A,Goto S,Hori T,Inoue I. Role of p38 mitogen-activated protein kinase on cerebral vasospasm after subarachnoid hemorrhage. Stroke 2004;35; 1466-1470.
[2]Dietrich HH and Dacey RG Jr.Molecular keys to the problems of cerebral vasospasm.Neurosurgery.2000;46(3):517-530.
[3]R H Wilkins. Cerebral vasospasm. Crit. Rev. Neurobiol.1990;6:51-77.
[4]Zarubin T, Han JH. Activation and signaling of the p38 MAP kinase pathway.Cell Research.2005;15:11-18.
[5]Sasaki T,Kasuya H,Onda H,Sasahara A,Goto S,Hori T,Inoue I. Role of p38 mitogen-activated protein kinase on cerebral vasospasm after subarachnoid hemorrhage.Stroke.2004;35:1466-1470.
[6]Raingeaud J, Gupta S, Rogers JS, et al. Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine[J].J BiolChem.1995;270(13):7420-7426.
[7]Thuerauf DJ, Arnold ND, Zechner D, et al. p38 Mi-togen-activated protein kinase mediates the transcriptional induction of the atrial natriuretic factor gene through a serum response element. A potential role for the transcription factor ATF6[J]. J Biol Chem.1998;273(32):20636-20643.
[8]Han J, Jiang Y, Li Z, et al. Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation[J]. Nature.1997;386(6622):296-299.
[9]Waskiewicz AJ,Johnson JC,Penn B,et al. Phosphorylation of the cap-binding protein eukeryotic translation initiation factor 4E by protein kinase Mnkl in vivo[J]. Mol Cell Biol.1999; 19(3):1871-1880.
[10]Dumont AS, Dumont RJ, Chow MM, Lin CL, Calisaneller T,Ley KF, Kassell NF, Lee KS. Cerebral vasospasm after subarachnoid hemorrhage:putative role of inflammation.Neurosurgery.2003;53:123-33.
[11]Guan Z, Buckman SY, Pentland AP, Templeton DJ, Morrison AR. Induction of cyclooxygenase-2 by the activated MEKK1→SEK1/MKK4→p38 mitogen-activated protein kinase pathway.J Biol Chem.1998;273:12901-8.
[12]Badger AM,Cook MN,Lark MW,et al.SB 203580 inhibits p38 mitogen-activated protein kinase, nitric oxide production, and inducible nitric oxide synthase in bovine cartilage-derived chondrocytes. J Immunol.1998; 161:467-73.
[13]Da Silva J,Pierrat B,Mary JL,Lesslauer W.Blockade of p38 mitogen-activated protein kinase pathway inhibits inducible nitric-oxide synthase expression in mouse astrocytes. J Biol Chem.1997; 272:28373-80.
[14]Pietersma A, Tilly BC, Gaestel M, et al. p38 mitogen activated protein kinase regulates endothelial VCAM-1 expression at the post-transcriptional level.Biochem Biophys Res Comm.1997;230:44-8.
[15]Lee JC, Laydon JT, McDonnell PC, et al. Identification and characterization of a novel protein kinase involved in the regulation of inflammatory cytokine biosynthesis.Nature.1994;372:739-46.
[16]Pluta RM, Oldfield EH, Boock RJ. Reversal and prevention of cerebral vasospasm by intracarotid infusions of nitric oxide donors in a primate model of subarachnoid hemorrhage. J Neurosurg.1997;87:746-51.
[17]Bombeli T, Karsan A, Tait JF, Harlan JM. Apoptotic vascular endothelial cells become procoagulant.Blood.1997;89:2429-42.
[18]Clower BR, Yamamoto Y, Cain L, Haines DE, Smith RR. Endothelial injury following experimental subarachnoid hemorrhage in rats:effects on brain blood flow.Anat Rec.1994;240:104-14.
[19]Borel CO, McKee A, Parra A, Haglund MM, Solan A, Prabhakar V,Sheng H,Warner DS,Niklason L. Possible role for vascular cell proliferation in cerebral vasospasm after subarachnoid hemorrhage.Stroke.2003;34:427-33.
[1]A.Y. Zubkov, R.E. Tibbs, K. Aoki, J.H. Zhang, Prevention of vasospasm in penetrating arteries with MAPK inhibitors in dog double-hemorrhage model, Surg. Neurol.54 (2000) 221-228.
[2]A. Pasqualin, Epidemiology and pathophysiology of cerebral vasospasm following subarachnoid hemorrhage, J. Neurosurg. Sci.42 (1998) 15-21.
[3]A.Y. Zubkov, A.I. Lewis, F.A. Raila, J. Zhang, A.D. Parent,Risk factors for the development of post-traumatic cerebral vasospasm, Surg. Neurol.53 (2000) 126-130.
[4]P.D. LeRoux, M.M. Haglund, M.R. Mayberg, H.R. Winn,Symptomatic cerebral vasospasm following tumor resection:report of two cases, Surg. Neurol.36 (1991) 25-31.
[5]S. Ries, U. Schminke, K. Fassbender, M. Daffertshofer, W.Steinke, M. Hennerici, Cerebrovascular involvement in the acute phase of bacterial meningitis, J. Neurol.244 (1997)51-55.
[6]N.W. Dorsch, Cerebral arterial spasm*/a clinical review, Br. J.Neurosurg.9 (1995) 403-412.
[7]A.D. Ecker, Does chronic cerebral vasospasm precede development and rupture of intracranial aneurysms? Mayo. Clin. Proc.59 (1984) 797.
[8]R.H. Wilkins, Cerebral vasospasm, Crit. Rev. Neurobiol.6(1990) 51-77.
[9]R.L. Macdonald, B.K. Weir, T.D. Runzer, M.G. Grace, J.M.Findlay, K. Saito, D.A. Cook, B.W. Mielke, K. Kanamaru,Etiology of cerebral vasospasm in primates, J. Neurosurg.75(1991) 415-424.
[10]M. Zuccarello, A.I. Lewis, S. Upputuri, J.B. Farmer, D.K.Anderson, Effect of remacemide hydrochloride on subarachnoid hemorrhage-induced vasospasm in rabbits, J. Neurotrauma.11(1994) 691-698.
[11]H. Zhang, B.K. Weir, R.L. Macdonald, L.S. Marton, N.J.Solenski, A.L. Kwan, K.S. Lee, Mechanisms of Ca2+ ielevation induced by erythrocyte components in endothelial cells, J. Pharmacol. Exp. Ther.277 (1996) 1501-1509.
[12]R.G. Hempelmann, R.H. Pradel, H.L. Barth, H.M. Mehdorn,A. Ziegler, Interactions between vasoconstrictors in isolated human cerebral arteries, Acta Neurochir. (Wien.) 139(1997)574-581.
[13]H. Masaoka, R. Suzuki, Y. Hirata, T. Emori, F. Marumo, K.Hirakawa, Raised plasma endothelin in aneurysmal subarachnoid haemorrhage, Lancet 2 (1989) 1402.
[14]H. Suzuki, S. Sato, Y. Suzuki, M. Oka, T. Tsuchiya, I. Iino, T.Yamanaka, N. Ishihara, S. Shimoda, Endothelin immunoreactivity in cerebrospinal fluid of patients with subarachnoid haemorrhage, Ann. Med.22 (1990) 233-236.
[15]T. Mima, M. Yanagisawa, T. Shigeno, A. Saito, K. Goto, K.Takakura, T. Masaki, Endothelin acts in feline and canine cerebral arteries from the adventitial side, Stroke 20(1989)1553-1556.
[16]K. Ide, K. Yamakawa, T. Nakagomi, T. Sasaki, I. Saito, H.Kurihara, M. Yosizumi, Y. Yazaki, K. Takakura, The role of endothelin in the pathogenesis of vasospasm following subarachnoid haemorrhage, Neurol. Res.11 (1989) 101-104.
[17]T. Asano, I. Ikegaki, Y. Suzuki, S. Satoh, M. Shibuya,Endothelin and the production of cerebral vasospasm in dogs,Biochem. Biophys. Res. Commun.159 (1989) 1345-1351.
[18]J.A. Alabadi, J.B. Salom, G. Torregrosa, F.J. Miranda, T. Jover,E. Alborch, Changes in the cerebrovascular effects of endothelin-1 and nicardipine after experimental subarachnoid hemorrhage,Neurosurgery 33 (1993) 707-714.
[19]S. Roux, B.M. Loffler, G.A. Gray, U. Sprecher, M. Clozel, J.P.Clozel, The role of endothelin in experimental cerebral vasospasm, Neurosurgery 37 (1995) 78-85.
[20]S. Roux, B.M. Loffler, G.A. Gray, U. Sprecher, M. Clozel, J.P.Clozel, The role of endothelin in experimental cerebral vasospasm,Neurosurgery 37 (1995) 78-85.
[21]M. Zuccarello, G.B. Soattin, A.I. Lewis, V. Breu, H. Hallak,R.M. Rapoport, Prevention of subarachnoid hemorrhage-induced cerebral vasospasm by oral administration of endothelin receptor antagonists, J. Neurosurg.84 (1996) 503-507.
[22]A. Hino, B.K. Weir, R.L. Macdonald, R.A. Thisted, C.J. Kim,L.M. Johns, Prospective, randomized, double-blind trial of BQ-123 and bosentan for prevention of vasospasm following subarachnoid hemorrhage in monkeys, J. Neurosurg.83 (1995)503-509.
[23]A.J. Gaw, R.M. Wadsworth, P.P. Humphrey, Neurotransmission in the sheep middle cerebral artery:modulation of responses by 5-HT and haemolysate, J. Cereb. Blood Flow Metab.10(1990) 409-416.
[24]N.A. Svendgaard, L. Edvinsson, C. Owman, C. Sahlin, Increased sensitivity of the basilar artery to norepinephrine and 5-hydroxytryptamine following experimental subarachnoid hemorrhage,Surg. Neurol.8 (1977) 191-195.
[25]A.Y. Zubkov, K. Ogihara, P. Tumu, G.D. Mandybur, A.I.Lewis, A.D. Parent, J.H. Zhang, Bloody cerebospinal fluid alters contraction of cultured arteries, Neurol. Res. 21 (1999) 553-558.
[26]P. Gaetani, C. Cafe, R. Baena, F. Tancioni, C. Torri, F. Tartara,F. Marzatico, Superoxide dismutase activity in cisternal cerebrospinal fluid after aneurysmal subarachnoid haemorrhage,Acta Neurochir. (Wien.) 139(1997) 1033-1037.
[27]K. Iwasa, D.H. Bernanke, R.R. Smith, Y. Yamamoto, Nonmuscle arterial constriction after subarachnoid hemorrhage:role of growth factors derived from platelets, Neurosurgery 32 (1993)619-624.
[28]C.D. Benham, P. Hess, R.W. Tsien, Two types of calcium channels in single smooth muscle cells from rabbit ear artery studied with whole-cell and single-channel recordings, Circ. Res.61 (1987) 110-116.
[29]T.B. Bolton, Mechanisms of action of transmitters and other substances on smooth muscle, Physiol. Rev.59 (1979) 606-718.
[30]C. van Breemen, P. Aaronson, Loutzenhiser, Sodium-calcium interactions in mammalian smooth muscle, Pharmacol. Rev.30(1978) 167-208.
[31]H. Liu, N. Sperelakis, Tyrosine kinases modulate the activity of single L-type calcium channels in vascular smooth muscle cells from rat portal vein, Can. J. Physiol. Pharmacol.75 (1997)1063-1068.
[32]H. Zhang, B. Weir, L.S. Marton, R.L. Macdonald, V. Bindokas,R.J. Miller, J.R. Brorson, Mechanisms of hemolysate-induced [Ca2+]i elevation in cerebral smooth muscle cells, Am. J.Physiol.269 (1995) H1874-H1890.
[33]E. Alborch, J.B. Salom, G. Torregrosa, Calcium channels in cerebral arteries, Pharmacol. Ther.68 (1995) 1-34.
[34]L. Missiaen, H. De Smedt, G. Droogmans, B. Himpens,Casteels, Calcium ion homeostasis in smooth muscle, Pharmacol.Ther.56 (1992) 191-231.
[35]B. Sima, B.K. Weir, R.L. Macdonald, H. Zhang, Extracellular nucleotide-induced [Ca2+]i elevation in rat basilar smooth muscle cells, Stroke 28 (1997) 2053-2058.
[36]S. Iwabuchi, L.S. Marton, J.H. Zhang, Role of protein tyrosine phosphorylation in erythrocyte lysate-induced intracellular free calcium concentration elevation in cerebral smooth-muscle cells,J. Neurosurg.90 (1999) 743-751.
[37]K. Aoki, A.Y. Zubkov, A.D. Parent, J.H. Zhang, Mechanism of ATP-induced [Ca2+](i) mobilization in rat basilar smooth muscle cells, Stroke 31 (2000) 1377-1384.
[38]P. Kim, Y. Yoshimoto, M. lino, S. Tomio, T. Kirino,Nonomura, Impaired calcium regulation of smooth muscle during chronic vasospasm following subarachnoid hemorrhage,J. Cereb. Blood Flow Metab.16 (1996) 334-341.
[39]N.F. Kassell, T. Sasaki, A.R. Colohan, G. Nazar, Cerebral vasospasm following aneurysmal subarachnoid hemorrhage,Stroke 16 (1985) 562-572.
[40]C.J. Kim, B. Weir, R.L. Macdonald, L.S. Marton, H. Zhang,Hemolysate inhibits L-type Ca2+channels in rat basilar smooth muscle cells, J. Vasc. Res.33 (1996) 258-264.
[41]K. Takenaka, H. Yamada, N. Sakai, T. Ando, Y. Okano, Y. Nozawa, Intracellular Ca2+changes in cultured vascular smooth muscle cells by treatment with various spasmogens,Neurol. Res.13 (1991) 168-172.
[42]C.J. Kim, B.K. Weir, R.L. Macdonald, H. Zhang, Erythrocyte lysate releases Ca2+ from IP3-sensitive stores and activates Ca2+-dependent K- channels in rat basilar smooth muscle cells,Neurol. Res.20 (1998) 23-30.
[43]Y. Takanashi, B.K. Weir, B. Vollrath, H. Kasuya, R.L.Macdonald, D. Cook, Time course of changes in concentration of intracellular free calcium in cultured cerebrovascular smooth muscle cells exposed to oxyhemoglobin, Neurosurgery 30 (1992)346-350.
[44]K. Takenaka, J. Kishino, H. Yamada, N. Sakai, H. Arita, Y.Okano, Y. Nozawa, DNA synthesis and intracellular calcium elevation in porcine cerebral arterial smooth muscle cells by cerebrospinal fluid from patients with subarachnoid haemorrhage,Neurol. Res.14 (1992) 330-334.
[45]C. Krueger, B. Weir, M. Nosko, D. Cook, S. Norris, Nimodipine and chronic vasospasm in monkeys:Part 2. Pharmacological studies of vessels in spasm, Neurosurgery 16 (1985) 137-140.
[46]K. Kohno, S. Sakaki, S. Ohue, Y. Kumon, K. Matsuoka,Intracellular calcium levels in canine basilar artery smooth muscle following experimental subarachnoid hemorrhage:an electron microscopic cytochemical study, Acta Neuropathol.(Berl) 81 (1991) 664-669.
[47]W.E. Bulter, J.W. Peterson, N.T. Zervas, K.G. Morgan,Intracellular calcium, myosin light chain phosphorylation, and contractile force in experimental cerebral vasospasm, Neurosurgery 38 (1996) 781-787.
[48]Y. Tanaka, T. Masuzawa, M. Saito, T. Yamada, K. Fujimoto,Change in Ca2+ sensitivity of cerebrovascular smooth muscle in experimental chronic cerebral vasospasm, Neurol. Med. Chir.(Tokyo) 38 (1998) 459-463.
[49]J.T. Stull, P.J. Lin, J.K. Krueger, J. Trewhella, G. Zhi, Myosin light chain kinase: functional domains and structural motifs,Acta Physiol. Scand.164 (1998) 471-482.
[50]A.P. Somlyo, J.W. Walker, Y.E. Goldman, D.R. Trentham, T.Kobayashi, Kitazawa, A.V. Somlyo, Inositol trisphosphate,calcium and muscle contraction, Philos. Trans. R. Soc. Lond.B Biol. Sci.320 (1988) 399-414.
[51]P.F. Dillon, M.O. Aksoy, S.P. Driska, R.A. Murphy, Myosin phosphorylation and the cross-bridge cycle in arterial smooth muscle, Science 211 (1981) 495-497.
[52]I. Kim, B.D. Leinweber, M. Morgalla, W.E. Butler, M. Seto, Y.Sasaki, J.W. Peterson, K.G. Morgan, Thin and thick filament regulation of contractility in experimental cerebral vasospasm,Neurosurgery 46 (2000) 440-446.
[53]T. Harada, M. Seto, Y. Sasaki, S. London, Z. Luo, M. Mayberg,The time course of myosin light-chain phosphorylation in bloodinduced vasospasm, Neurosurgery 36 (1995)1178-1182.
[54]Y. Suzuki, M. Shibuya, M. Takayasu, T. Asano, I. Ikegaki, S.Satoh, M. Saito, H. Hidaka, Protein kinase activity in canine basilar arteries after subarachnoid hemorrhage, Neurosurgery 22(1988) 1028-1031.
[55]M.J. Berridge, Inositol trisphosphate and calcium signalling,Nature 361 (1993) 315-325.
[56]J.W. Walker, A.V. Somlyo, Y.E. Goldman, A.P. Somlyo, D.R.Trentham, Kinetics of smooth and skeletal muscle activation bylaser pulse photolysis of caged inositol 1,4,5-trisphosphate,Nature 327 (1987) 249-252.
[57]B. Vollrath, B.K. Weir, D.A. Cook, Hemoglobin causes release of inositol trisphosphate from vascular smooth muscle, Biochem.Biophys. Res. Commmun.171 (1990)506-511.
[58]B.A. Vollrath, B.K. Weir, R.L. Macdonald, D.A. Cook,Intracellular mechanisms involved in the responses of cerebrovascular smooth-muscle cells to hemoglobin, J. Neurosurg.80(1994) 261-268.
[59]B. Sima, L. MacDonald, L.S. Marton, B. Weir, J. Zhang, Effect of P2-purinoceptor antagonists on hemolysate-induced and adenosine 5?-triphosphate-induced contractions of dog basilar artery in vitro, Neurosurgery 39 (1996)815-821.
[60]Y. Nishizuka, Membrane phospholipid degradation and protein kinase C for cell signalling, Neurosci. Res.15 (1992) 3-5.
[61]K.P. Huang, The mechanism of protein kinase C activation,Trends Neurosci.12 (1989) 425-432.
[62]T. Matsui, Y. Takuwa, H. Johshita, K. Yamashita, T. Asano,Possible role of protein kinase C-dependent smooth muscle contraction in the pathogenesis of chronic cerebral vasospasm, J.Cereb. Blood Flow Metab.11 (1991) 143-149.
[63]W.H. Moolenaar, W. Kruijer, B.C. Tilly, I. Verlaan, A.J.Bierman, S.W. de Laat, Growth factor-like action of phosphatidic acid, Nature 323 (1986) 171-173.
[64]C.L. Yu, M.H. Tsai, D.W. Stacey, Cellular ras activity and phospholipid metabolism, Cell 52 (1988) 63-71.
[65]C.F. Huang, M.C. Cabot, Phorbol diesters stimulate the accumulation of phosphatidate, phosphatidylethanol, and diacylglycerol in three cell types. Evidence for the indirect formation of phosphatidylcholine-derived diacylglycerol by a phospholipase D pathway and direct formation of diacylglycerol by a phospholipase C pathway, J. Biol. Chem.265 (1990) 14858-14863.
[66]E.F. LaBelle, R.M. Fulbright, R.J. Barsotti, H. Gu, E. Polyak,Phospholipase D is activated by G protein and not by calcium ions in vascular smooth muscle, Am. J. Physiol.270 (1996)H1031-H1037.
[67]D.T. Ward, J. Ohanian, A.M. Heagerty, V. Ohanian, Phospholipase D-induced phosphatidate production in intact small arteries during noradrenaline stimulation: involvement of both G-protein and tyrosine-phosphorylation-linked pathways, Biochem.J.307 (1995) 451-456.
[68]A.W. Jones, S.D. Shukla, B.B. Geisbuhler, Stimulation of phospholipase D activity and phosphatidic acid production by norepinephrine in rat aorta, Am. J. Physiol.264 (1993) C609-C616.
[69]J.H. Exton, Signaling through phosphatidylcholine breakdown,J. Biol. Chem.265 (1990) 1-4.
[70]M.M. Billah, J.C. Anthes, The regulation and cellular functions of phosphatidylcholine hydrolysis, Biochem. J.269 (1990) 281-291.
[71]E.J. Freeman, G.M. Chisolm, E.A. Tallant, Role of calcium and protein kinase C in the activation of phospholipase D by angiotensin Ⅱ in vascular smooth muscle cells, Arch. Biochem. Biophys.319 (1995) 84-92.
[72]D.A. Cook, B. Vollrath, Free radicals and intracellular events associated with cerebrovascular spasm, Cardiovasc. Res.30(1995) 493-500.
[73]T. Matsui, Y. Takuwa, H. Kaizu, T. Asano, Possible involvement of C-kinase in occurrence of chronic cerebral vasospasm after subarachnoid hemorrhage, Adv. Exp. Med. Biol.331(1993) 177-182.
[74]Sato M, Tani E, Fujikawa H, Kaibuchi K. Involvement of Rhokinase-mediated phosphorylation of myosin light chain in enhancement of cerebral vasospasm. Circ Res.2000;87:195-200.
[75]Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T,Tamakawa H, Yamagami K, Inui J, Maekawa M, et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. 1997;389:990-994.26.
[76]Chrissobolis S, Sobey CG. Evidence that Rho-kinase activity contributes to cerebral vascular tone in vivo and is enhanced during chronic hypertension comparison with protein kinase C. Circ Res.2001;88:774-779.
[77]Madaule P, Axel R. A novel ras2related gene family. Cell,1985,41:31-40.
[78]Kaibuchi K, Kuroda S, Amano M. Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells.Annu Rev Biochem,1999, 68:459-486.
[79]Riento K, RidleyAJ. Rocks:multifunctional kinases in cell behav2 iour. Nat RevMol Cell Biol,2003,4:446-456.
[80]Matsui T, AmanoM, Yamamoto T, et al. Rho2associated kinase, a novel serine/ threonine kinase, as a putative target for small GTP binding p rotein Rho. EMBO J, 1996,15:2208-2216.
[81]Tosaka M,Okajima F,Hashiba Y, et al. Sphingosine 12phosphate contracts canine basilar arteries in vitro and in vivo:possible role in pathogenesis of cerebral vasospasm [J].Stroke,2001,32 (12):2913-2919.
[82]Wickman G,Lan C,Vollrath B. Functional roles of the RhoP Rho kinase pathway and protein kinase C in the regulation of cerebrovascular constriction mediated by hemoglobin, relevance to subarachnoid hemorrhage and vasospasm[J]. Circ Res,2003,92:809-816.
[83]Lan C,Das D,Wloskowicz A, et al. Endothelin21 modulates hemoglobin2mediated signaling in cerebrovascular smooth muscle via RhoAPRho kinase and protein kinase C [J]. Am J Physiol Heart Circ Physiol,2004,286 (1):H165-173.
[84]Nakamura K, Nishimura J, Hirano K, et al. Hydroxyfasudil, an active metabolite of fasudil hydrochloride, relaxes the rabbit basilar artery by disinhibition of myosin light chain phosphatase. J CerebBlood FlowMetab,2001,21:876-885.
[85]G. Whitney, D. Throckmorton, C. Isales, Y. Takuwa, J. Yeh, H.Rasmussen, C. Brophy, Kinase activation and smooth muscle contraction in the presence and absence of calcium, J. Vasc.Surg.22 (1995) 37-44.
[86]M. Ikebe, D.J. Hartshorne, M. Elzinga, Phosphorylation of the 20 000-dalton light chain of smooth muscle myosin by the calcium-activated, phospholipid-dependent protein kinase. Phosphorylation sites and effects of phosphorylation, J. Biol. Chem. 262 (1987) 9569-9573.
[87]T. Matsui, M. Sugawa, H. Johshita, Y. Takuwa, T. Asano,Activation of the protein kinase C-mediated contractile system in canine basilar artery undergoing chronic vasospasm, Stroke 22(1991) 1183-1187.
[88]S. Nishizawa, N. Nezu, K. Uemura, Direct evidence for a key role of protein kinase C in the development of vasospasm after subarachnoid hemorrhage, J. Neurosurg.76 (1992) 635-639..
[89]S. Nishizawa, J.W. Peterson, I. Shimoyama, K. Uemura,Relation between protein kinase C and calmodulin systems in cerebrovascular contraction:investigation of the pathogenesis of vasospasm after subarachnoid hemorrhage, Neurosurgery 31(1992) 711-716.
[90]M. Sako, J. Nishihara, S. Ohta, J. Wang, S. Sakaki, Role of protein kinase C in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage, J. Cereb. Blood Flow Metab.13(1993)247-254.
[91]Y. Takuwa, T. Matsui, Y. Abe, T. Nagafuji, K. Yamashita, T.Asano, Alterations in protein kinase C activity and membrane lipid metabolism in cerebral vasospasm after subarachnoid hemorrhage, J. Cereb. Blood Flow Metab.13 (1993) 409-415.
[92]M. Zuccarello, C.L. Bonasso, A.I. Lewis, N. Sperelakis, R.M.Rapoport, Relaxation of subarachnoid hemorrhage-induced spasm of rabbit basilar artery by the K+-channel activator cromakalim, Stroke 27 (1996) 311-316.
[93]E. Tachibana, T. Harada, M. Shibuya, K. Saito, M. Takayasu,Y. Suzuki, J. Yoshida, Intra-arterial infusion of fasudil hydrochloride for treating vasospasm following subarachnoid haemorrhage,Acta Neurochir. (Wien.) 141 (1999) 13-19.
[94]M.D. Hollenberg, Tyrosine kinase pathways and the regulation of smooth muscle contractility, Trends Pharmacol. Sci.15 (1994)108-114.
[95]N. Kaplan, J. Di Salvo, Coupling between [arginine8]-vasopressin-activated increases in protein tyrosine phosphorylation and cellular calcium in A7r5 aortic smooth muscle cells, Arch.Biochem. Biophys.326 (1996) 271-280.
[96]T. Gokita, Y. Miyauchi, M.K. Uchida, Effects of tyrosine kinase inhibitor, genistein, and phosphotyrosine-phosphatase inhibitor,orthovanadate, on Ca2+-free contraction of uterine smooth muscle of the rat, Gen. Pharmacol.25 (1994) 1673-1677.
[97]W. Abebe, D.K. Agrawal, Role of tyrosine kinases in norepinephrine-induced contraction of vascular smooth muscle, J.Cardiovasc. Pharmacol.26 (1995) 153-159.
[98]S. Lev, H. Moreno, R. Martinez, P. Canoll, E. Peles, J.M. Musacchio, G.D. Plowman, B. Rudy, J. Schlessinger, Protein tyrosine kinase PYK2 involved in Ca2+-induced regulation of ion channel and MAP kinase functions, Nature 376 (1995) 737-745.
[99]S.A. Siegelbaum, Channel regulation. Ion channel control by tyrosine phosphorylation, Curr. Biol.4 (1994) 242-245.
[100]M. Watanabe, M. Doi, K. Sasaki, A. Ogawa, Modulatory role of protein tyrosine kinase activation in the receptor-induced contractions of the bovine cerebral artery, Neurol. Med. Chir.(Tokyo) 38 (1998) 75-81.
[101]A.Y. Zubkov, K.S. Rollins, A.D. Parent, J. Zhang, R.M. Bryan,Mechanism of endothelin-1-induced contraction in rabbit basilar artery, Stroke 31 (2000) 526-533.
[102]L.S. Marton, B.K. Weir, H. Zhang, Tyrosine phosphorylation and [Ca2+]i elevation induced by hemolysate in bovine endothelial cells:implications for cerebral vasospasm, Neurol. Res.18 (1996) 349-353.
[103]C.J. Kim, B.K. Weir, R.L. Macdonald, H. Zhang, Erythrocyte lysate releases Ca2+from IP3-sensitive stores and activates Ca2+-dependent K+ channels in rat basilar smooth muscle cells, Neurol. Res.20 (1998) 23-30.
[104]B. Vollrath, D. Cook, J. Megyesi, J.M. Findlay, H. Ohkuma,Novel mechanism by which hemoglobin induces constriction of cerebral arteries, Eur. J. Pharmacol.361 (1998)311-319.
[105]T.J. Childs, A.S. Mak, MAP kinases from bovine brain:purification and characterization, Biochem. Cell Biol.71 (1993)544-555.
[106]K.K. Griendling, M. Ushio-Fukai, B. Lassegue, R.W. Alexander,Angiotensin II signaling in vascular smooth muscle. New concepts, Hypertension 29 (1997) 366-373.
[107]M.H. Watson, S.L. Venance, S.C. Pang, A.S. Mak, Smooth muscle cell proliferation. Expression and kinase activities of p34cdc2 and mitogen-activated protein kinase homologues, Circ.Res.73 (1993) 109-117.
[108]H. Sun, N.K. Tonks, D. Bar-Sagi, Inhibition of Ras-induced DNA synthesis by expression of the phosphatase MKP-1,Science 266 (1994) 285-288.
[109]S.S. Katoch, R.S. Moreland, Agonist and membrane depolarization induced activation of MAP kinase in the swine carotid artery, Am. J. Physiol.269 (1995) H222-H229.
[110]A.Y. Zubkov, K. Ogihara, P. Tumu, A. Patlolla, A.I. Lewis,A.D. Parent, J. Zhang, Mitogen-activated protein kinase mediation of hemolysate-induced contraction in rabbit basilar artery,J. Neurosurg.90 (1999) 1091-1097.
[111]H. Fujikawa, E. Tani, I. Yamaura, I. Ozaki, K. Miyaji, M. Sato,K. Takahashi, S. Imajoh-Ohmi, Activation of protein kinases in canine basilar artery in vasospasm, J. Cereb. Blood Flow Metab.19 (1999) 44-52.
[112]P. Rodriguez-Viciana, P.H. Warne, B. Vanhaesebroeck, M.D.Waterfield, J. Downward, Activation of phosphoinositide 3-kinase by interaction with Ras and by point mutation, EMBO J.15 (1996) 2442-2451.
[113]J. Suga, Y. Yoshimasa, K. Yamada, Y. Yamamoto, G. Inoue,M. Okamoto, M. Hayashi, Shigemoto, A. Kosaki, H. Kuzuya,K. Nakao, Differential activation of mitogen-activated protein kinase by insulin and epidermal growth factor in 3T3-L1 adipocytes:a possible involvement of PI3-kinase in the activation of the MAP kinase by insulin, Diabetes 46 (1997) 735-741.
[114]K. Osuka, Y. Suzuki, T. Tanazawa, K. Hattori, N. Yamamoto,M. Takayasu, M. Shibuya, J. Yoshida, Interleukin-6 and development of vasospasm after subarachnoid haemorrhage,Acta Neurochir. (Wien.) 140 (1998) 943-951.
[115]I. Guillet-Deniau, A.F. Burnol, J. Girard, Identification and localization of a skeletal muscle secrotonin 5-HT2A receptor coupled to the Jak/STAT pathway, J. Biol. Chem.272 (1997)14825-14829.
[116]D.W. Love, A.J. Whatmore, P.E. Clayton, C.M. Silva, Growth hormone stimulation of the mitogen-activated protein kinase pathway is cell type specific, Endocrinology 139 (1998) 1965-1971.
[117]L.P. Adam, J.R. Haeberle, D.R. Hathaway, Phosphorylation of caldesmon in arterial smooth muscle, J. Biol. Chem.264 (1989)7698-7703.
[118]L.P. Adam, D.R. Hathaway, Identification of mitogen-activated protein kinase phosphorylation sequences in mammalian h-Caldesmon, FEBS Lett.322 (1993) 56-60.
[119]J.J. Earley, X. Su, R.S. Moreland, Caldesmon inhibits active crossbridges in unstimulated vascular smooth muscle:an antisense oligodeoxynucleotide approach, Circ. Res.83 (1998) 661-667.
[120]Z. Wang, H. Jiang, Z.Q. Yang, S. Chacko, Both N-terminal myosin-binding and C-terminal actin-binding sites on smooth muscle caldesmon are required for caldesmon-mediated inhibition of actin filament velocity, Proc. Natl. Acad. Sci. USA 94(1997)11899-11904.
[121]T. Itoh, A. Suzuki, Y. Watanabe, T. Mino, M. Naka, T. Tanaka,A calponin peptide enhances Ca2+ sensitivity of smooth muscle contraction without affecting myosin light chain phosphorylation,J. Biol. Chem.270 (1995) 20400-20403.
[122]M. Doi, H. Kasuya, B. Weir, D.A. Cook, A. Ogawa, Reduced expression of calponin in canine basilar artery after subarachnoid haemorrhage, Acta Neurochir. (Wien.) 139 (1997) 77-81.
[123]C.B. Menice, J. Hulvershorn, L.P. Adam, C.A. Wang, K.G.Morgan, Calponin and mitogen-activated protein kinase signaling in differentiated vascular smooth muscle, J. Biol. Chem.272(1997) 25157-25161.
[124]Z. Xiong, N. Sperelakis, C. Fenoglio-Preiser, Regulation of Ltype calcium channels by cyclic nucleotides and phosphorylation in smooth muscle cells from rabbit portal vein, J. Vasc. Res.31(1994) 271-279.
[125]P. de Lanerolle, M. Nishikawa, D.A. Yost, R.S. Adelstein,Increased phosphorylation of myosin light chain kinase after an increase in cyclic AMP in intact smooth muscle, Science 223(1984) 1415-1417.
[126]R.V. Vegesna, J. Diamond, Effects of isoproterenol and forskolin on tension, cyclic AMP levels, and cyclic AMP dependent protein kinase activity in bovine coronary artery,Can. J. Physiol. Pharmacol.62 (1984) 1116-1123.
[127]H. Todo, S. Ohta, J. Wang, H. Ichikawa, S. Ohue, Y. Kumon, S.Sakaki, Impairment in biochemical level of arterial dilative capability of a cyclic nucleotides-dependent pathway by induced vasospasm in the canine basilar artery, J. Cereb. Blood Flow Metab.18 (1998) 808-817.
[128]D.H. Edwards, J.V. Byrne, T.M. Griffith, The effect of chronic subarachnoid hemorrhage on basal endothelium-derived relaxing factor activity in intrathecal cerebral arteries, J. Neurosurg.76 (1992) 830-837.
[129]R.L. Macdonald, B.K. Weir, A review of hemoglobin and the pathogenesis of cerebral vasospasm, Stroke 22 (1991) 971-982.
[130]C.G. Sobey, F.M. Faraci, Effects of a novel inhibitor of guanylyl cyclase on dilator responses of mouse cerebral arterioles, Stroke28 (1997) 837-842.
[131]P. Kim, V.B. Schini, T.M.J. Sundt, P.M. Vanhoutte, Reduced production of cGMP underlies the loss of endothelium-dependent relaxations in the canine basilar artery after subarachnoid hemorrhage, Circ. Res.70 (1992) 248-256.
[132]H. Kasuya, B.K. Weir, M. Nakane, J.S. Pollock, L. Johns, L.S.Marton, K. Stefansson, Nitric oxide synthase and guanylate cyclase levels in canine basilar artery after subarachnoid hemorrhage, J. Neurosurg.82 (1995) 250-255.
[133]P. Kim, Loss of relaxations, metabolic failure and increased calcium permeability of smooth muscle during chronic cerebral vasospasm, J. Auton. Nerv. Syst.49 (Suppl.) (1994) S157-S162.
[134]C.G. Sobey, F.M. Faraci, Subarachnoid haemorrhage:what happens to the cerebral arteries? Clin. Exp. Pharmacol. Physiol.25 (1998) 867-876.
[135]D.R. Harder, P. Dernbach, A. Waters, Possible cellular mechanism for cerebral vasospasm after experimental subarachnoid hemorrhage in the dog, J. Clin. Invest.80 (1987) 875-880.
[136]R. Tibbs, A. Zubkov, K. Aoki, T. Meguro, A. Badr, A. Parent,J. Zhang, Effects of mitogen-activated protein kinase inhibitors on cerebral vasospasm in a double-hemorrhage model in dogs, J.Neurosurg.93 (2000) 1041-1047.
[137]H. Onda, H. Kasuya, K. Takakura, T. Hori, T. Imaizumi, T.Takeuchi, I. Inoue, J. Takeda, Identification of genes differentially expressed in canine vasospastic cerebral arteries after subarachnoid hemorrhage, J. Cereb. Blood Flow Metab.19(1999) 1279-1288.
[138]Y. Aihara, H. Kasuya, H. Onda, T. Hori, J. Takeda, F.M.Faraci, Quantitative analysis of gene expressions related to inflammation in canine spastic artery after subarachnoid hemorrhage editorial comment, Stroke 32 (2001) 212-217.
1. Brewster, J.L., et al., An osmosensing signal transduction pathway in yeast. Science,1993.259(5102):p.1760-3.
2. Han, J., et al., A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science,1994.265(5173):p.808-11.
3. Hale, K.K., et al., Differential expression and activation of p38 mitogen-activated protein kinase alpha, beta, gamma, and delta in inflammatory cell lineages. Journal of Immunology,1999.162(7):p.4246-52.
4. Rouse, J., et al., A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins. Cell,1994.78(6):p.1027-37.
5. Shapiro, L., et al., Interleukin 18 stimulates HIV type 1 in monocytic cells. Proceedings of the National Academy of Sciences of the United States of America,1998.95(21):p.12550-5.
6. Foltz, I.N., et al., Hemopoietic growth factors with the exception of interleukin-4 activate the p38 mitogen-activated protein kinase pathway. Journal of Biological Chemistry,1997.272(6):p.3296-301.
7. Sweeney, G., et al., An inhibitor of p38 mitogen-activated protein kinase prevents insulin-stimulated glucose transport but not glucose transporter translocation in 3T3-L1 adipocytes and L6 myotubes. Journal of Biological Chemistry,1999.274(15):p.10071-8.
8. Heidenreich, K.A. and J.L. Kummer, Inhibition of p38 mitogen-activated protein kinase by insulin in cultured fetal neurons. Journal of Biological Chemistry,1996.271(17):p.9891-4.
9. Enslen, H., J. Raingeaud, and R.J. Davis, Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6. Journal of Biological Chemistry,1998.273(3):p.1741-8.
10. Jiang, Y., et al., Characterization of the structure and function of the fourth member of p38 group mitogen-activated protein kinases, p38delta. Journal of Biological Chemistry,1997.272(48):p.30122-8.
11. Ge, B., et al., MAPKK-independent activation of p38alpha mediated by TAB1-dependent autophosphorylation of p38alpha. Science,2002.295(5558): p.1291-4.
12. Bagrodia, S., et al., Cdc42 and PAK-mediated signaling leads to Jun kinase and p38 mitogen-activated protein kinase activation. Journal of Biological Chemistry,1995.270(47):p.27995-8.
13. Zhang, S., et al., Rho family GTPases regulate p38 mitogen-activated protein kinase through the downstream mediator Pakl. Journal of Biological Chemistry,1995.270(41):p.23934-6.
14. Nick, J.A., et al., Common and distinct intracellular signaling pathways in human neutrophils utilized by platelet activating factor and FMLP. Journal of Clinical Investigation,1997.99(5):p.975-86.
15. Manser, E., et al., A brain serine/threonine protein kinase activated by Cdc42 and Racl. Nature,1994.367(6458):p.40-6.
16. Jackson, P.F. and J.L. Bullington, Pyridinylimidazole based p38 MAP kinase inhibitors. Curr Top Med Chem,2002.2(9):p.1011-20.
17. Cirillo, P.F., C. Pargellis, and J. Regan, The non-diaryl heterocycle classes of p38 MAP kinase inhibitors. Curr Top Med Chem,2002.2(9):p.1021-35.
18. Lee, J.C., et al., Inhibition of p38 MAP kinase as a therapeutic strategy. Immunopharmacology,2000.47(2-3):p.185-201.
19. Thuerauf, D.J., et al., p38 Mitogen-activated protein kinase mediates the transcriptional induction of the atrial natriuretic factor gene through a serum response element. A potential role for the transcription factor ATF6. Journal of Biological Chemistry,1998.273(32):p.20636-43.
20. Ferrer, I., et al., Early modifications in the expression of mitogen-activated protein kinase (MAPK/ERK), stress-activated kinases SAPK/JNK and p38, and their phosphorylated substrates following focal cerebral ischemia. Acta Neuropathol,2003.105(5):p.425-37.
21. Borsch-Haubold, A.G., R.M. Kramer, and S.P. Watson, Phosphorylation and activation of cytosolic phospholipase A2 by 38-kDa mitogen-activated protein kinase in collagen-stimulated human platelets. European Journal of Biochemistry,1997.245(3):p.751-9.
22. Guan, Z., et al., Induction of cyclooxygenase-2 by the activated MEKKI --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway. Journal of Biological Chemistry,1998.273(21):p.12901-8.
23. Badger, A.M., et al., SB 203580 inhibits p38 mitogen-activated protein kinase, nitric oxide production, and inducible nitric oxide synthase in bovine cartilage-derived chondrocytes. Journal of Immunology,1998.161(1):p. 467-73.
24. Da Silva, J., et al., Blockade of p38 mitogen-activated protein kinase pathway inhibits inducible nitric-oxide synthase expression in mouse astrocytes. Journal of Biological Chemistry,1997.272(45):p.28373-80.
25. Craxton, A., et al., p38 MAPK is required for CD40-induced gene expression and proliferation in B lymphocytes. Journal of Immunology,1998.161(7):p. 3225-36.
26. Pietersma, A., et al., p38 mitogen activated protein kinase regulates endothelial VCAM-1 expression at the post-transcriptional level. Biochemical and Biophysical Research Communications,1997.230(1):p.44-8.
27. Lee, J.C., et al., A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature,1994.372(6508):p.739-46.
28. Xia, Z., et al., Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science,1995.270(5240):p.1326-31.
29. Juo, P., et al., Fas activation of the p38 mitogen-activated protein kinase signalling pathway requires ICE/CED-3 family proteases. Molecular and Cellular Biology,1997.17(1):p.24-35.
30. Huang, S., et al., Apoptosis signaling pathway in T cells is composed of ICE/Ced-3 family proteases and MAP kinase kinase 6b. Immunity,1997.6(6): p.739-49.
31. Cardone, M.H., et al., The regulation of anoikis:MEKK-1 activation requires cleavage by caspases. Cell,1997.90(2):p.315-23.
32. Ziegler-Heitbrock, H.W., et al., In vitro desensitization to lipopolysaccharide suppresses tumour necrosis factor, interleukin-1 and interleukin-6 gene expression in a similar fashion. Immunology,1992.75(2):p.264-8.
33. Koike, N., et al., Effects of adding P38 mitogen-activated protein-kinase inhibitor to celsior solution in canine heart transplantation from non-heart-beating donors. Transplantation,2004.77(2):p.286-92.
34. 王雨,田伏洲,汤礼军,等.p38信号转导途径对离体肝脏缺血再灌注损伤的影响[J].中华肝脏病杂志,2003,11(3)：p.170-2.
35. 王雨,汤礼军,戴睿夫,等.p38 MAPK信号转导途径对缺血再灌注早期离体肝脏细胞因子表达的影响[J].中国普外基础与临床杂志,2009,16(6)：p.443-8.
36. Kim, E.S., M.S. Kim, and A. Moon, TGF-beta-induced upregulation of MMP-2 and MMP-9 depends on p38 MAPK, but not ERK signaling in MCF10A human breast epithelial cells. International Journal of Oncology, 2004.25(5):p.1375-82.
37. Wang, W.H., R.L. Hullinger, and O.M. Andrisani, Hepatitis B virus X protein via the p38MAPK pathway induces E2F1 release and ATR kinase activation mediating p53 apoptosis. Journal of Biological Chemistry,2008.283(37):p. 25455-67.
38. Kim, M.S., et al., p38 kinase is a key signaling molecule for H-Ras-induced cell motility and invasive phenotype in human breast epithelial cells. Cancer Research,2003.63(17):p.5454-61.
39. Ke, Z., et al., MMP-2 mediates ethanol-induced invasion of mammary epithelial cells over-expressing ErbB2. International Journal of Cancer,2006. 119(1):p.8-16.
40. Huang, X., et al., Genistein inhibits p38 map kinase activation, matrix metalloproteinase type 2, and cell invasion in human prostate epithelial cells. Cancer Research,2005.65(8):p.3470-8.
41. Yu, J., et al., p38 Mitogen-activated protein kinase regulation of endothelial cell migration depends on urokinase plasminogen activator expression. Journal of Biological Chemistry,2004.279(48):p.50446-54.
42. Shin, B.A., et al., P38 MAPK pathway is involved in the urokinase plasminogen activator expression in human gastric SNU-638 cells. Oncology Reports,2003.10(5):p.1467-71.
43. Greenberg, A.K., et al., Selective p38 activation in human non-small cell lung cancer. American Journal of Respiratory Cell and Molecular Biology,2002. 26(5):p.558-64.
44. Liao, P., et al., The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy. Proceedings of the National Academy of Sciences of the United States of America,2001.98(21):p.12283-8.
45. Zhang, S., et al., The role of the Grb2-p38 MAPK signaling pathway in cardiac hypertrophy and fibrosis. Journal of Clinical Investigation,2003. 111(6):p.833-41.
46. Gao, F., et al., p38 MAPK inhibition reduces myocardial reperfusion injury via inhibition of endothelial adhesion molecule expression and blockade of PMN accumulation. Cardiovascular Research,2002.53(2):p.414-22.
47. Das, D.K., et al., Reactive oxygen species function as second messenger during ischemic preconditioning of heart. Molecular and Cellular Biochemistry,1999.196(1-2):p.59-67.
48. Stern, M.P., Diabetes and cardiovascular disease. The "common soil" hypothesis. Diabetes,1995.44(4):p.369-74.
49. Ju, H., et al., p38 MAPK inhibitors ameliorate target organ damage in hypertension:Part 1. p38 MAPK-dependent endothelial dysfunction and hypertension. Journal of Pharmacology and Experimental Therapeutics,2003. 307(3):p.932-8.
50. Paris, D., et al., Cholesterol modulates vascular reactivity to endothelin-1 by stimulating a pro-inflammatory pathway. Biochemical and Biophysical Research Communications,2000.274(2):p.553-8.
51. Bokemeyer, D., A. Sorokin, and M.J. Dunn, Multiple intracellular MAP kinase signaling cascades. Kidney International,1996.49(5):p.1187-98.
52. Kyaw, M., et al., Antioxidants inhibit JNK and p38 MAPK activation but not ERK 1/2 activation by angiotensin Ⅱ in rat aortic smooth muscle cells. Hypertension Research,2001.24(3):p.251-61.
53. Sun, A., et al., P38 MAP kinase is activated at early stages in Alzheimer's disease brain. Experimental Neurology,2003.183(2):p.394-405.
54. Otth, C., et al., Modulation of the JNK and p38 pathways by cdk5 protein kinase in a transgenic mouse model of Alzheimer's disease. Neuroreport,2003. 14(18):p.2403-9.
55. 刘华,徐祖才,夏杰,等.p38 MAPK信号通路在癫大鼠海马结构中的激活.重庆医学,2007,36：p.1259-1260.
56. Poolos, N.P., J.B. Bullis, and M.K. Roth, Modulation of h-channels in hippocampal pyramidal neurons by p38 mitogen-activated protein kinase. Journal of Neuroscience,2006.26(30):p.7995-8003.
1. Zhou, C., et al., Caspase inhibitors prevent endothelial apoptosis and cerebral vasospasm in dog model of experimental subarachnoid hemorrhage. Journal of Cerebral Blood Flow and Metabolism,2004.24(4):p.419-31.
2. Dietrich, H.H. and R.G Dacey, Jr., Molecular keys to the problems of cerebral vasospasm. Neurosurgery,2000.46(3):p.517-30.
3. Zubkov, A.Y., A. Nanda, and J.H. Zhang, Signal transduction pathways in cerebral vasospasm. Pathophysiology,2003.9(2):p.47-61.
4. Zhou, M.L., et al., Expression of Toll-like receptor 4 in the basilar artery after experimental subarachnoid hemorrhage in rabbits:a preliminary study. Brain Research,2007.1173:p.110-6.
5. Chen, G, et al., Potential role of JAK2 in cerebral vasospasm after experimental subarachnoid hemorrhage. Brain Research,2008.1214:p. 136-44.
6. Irving, E.A. and M. Bamford, Role of mitogen-and stress-activated kinases in ischemic injury. Journal of Cerebral Blood Flow and Metabolism,2002.22(6): p.631-47.
7. Yamaguchi, M., et al., Ras protein contributes to cerebral vasospasm in a canine double-hemorrhage model. Stroke,2004.35(7):p.1750-5.
8. Varsos, V.G., et al., Delayed cerebral vasospasm is not reversible by aminophylline, nifedipine, or papaverine in a "two-hemorrhage" canine model. Journal of Neurosurgery,1983.58(1):p.11-7.
9. Zhen, X., et al., The p38 mitogen-activated protein kinase is involved in associative learning in rabbits. Journal of Neuroscience,2001.21(15):p. 5513-9.
10. Zhou, M.L., et al., Comparison between one- and two-hemorrhage models of cerebral vasospasm in rabbits. Journal of Neuroscience Methods,2007. 159(2):p.318-24.
11. Zarubin, T. and J. Han, Activation and signaling of the p38 MAP kinase pathway. Cell Research,2005.15(1):p.11-8.
12. Kumar, S., et al., Novel homologues of CSBP/p38 MAP kinase:activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles. Biochemical and Biophysical Research Communications,1997.235(3):p. 533-8.
13. Parker, C.G., et al., Identification of stathmin as a novel substrate for p38 delta. Biochemical and Biophysical Research Communications,1998.249(3):p. 791-6.
14. Jiang, Y., et al., Characterization of the structure and function of the fourth member of p38 group mitogen-activated protein kinases, p38delta. Journal of Biological Chemistry,1997.272(48):p.30122-8.
15. Sun, H., et al., MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo. Cell,1993. 75(3):p.487-93.
1. Treggiari-Venzi, M.M., P.M. Suter, and J.A. Romand, Review of medical prevention of vasospasm after aneurysmal subarachnoid hemorrhage:a problem of neurointensive care. Neurosurgery,2001.48(2):p.249-61; discussion 261-2.
2. Zhou, C., et al., Caspase inhibitors prevent endothelial apoptosis and cerebral vasospasm in dog model of experimental subarachnoid hemorrhage. Journal of Cerebral Blood Flow and Metabolism,2004.24(4):p.419-31.
3. Dietrich, H.H. and R.G. Dacey, Jr., Molecular keys to the problems of cerebral vasospasm. Neurosurgery,2000.46(3):p.517-30.
4. Dumont, A.S., et al., Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation. Neurosurgery,2003.53(1):p.123-33; discussion 133-5.
5. Lee, J.C., et al., A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature,1994.372(6508):p.739-46.
6. Ridley, S.H., et al., Actions of IL-1 are selectively controlled by p38 mitogen-activated protein kinase:regulation of prostaglandin H synthase-2, metalloproteinases, and IL-6 at different levels. Journal of Immunology,1997. 158(7):p.3165-73.
7. Ohashi, N., et al., Role of p38 mitogen-activated protein kinase in neointimal hyperplasia after vascular injury. Arteriosclerosis, Thrombosis, and Vascular Biology,2000.20(12):p.2521-6.
8. Varsos, V.G, et al., Delayed cerebral vasospasm is not reversible by aminophylline, nifedipine, or papaverine in a "two-hemorrhage"canine model. Journal of Neurosurgery,1983.58(1):p.11-7.
9. Zhen, X., et al., The p38 mitogen-activated protein kinase is involved in associative learning in rabbits. Journal of Neuroscience,2001.21(15):p. 5513-9.
10. Bombeli, T., et al., Apoptotic vascular endothelial cells become procoagulant. Blood,1997.89(7):p.2429-42.
11. Guan, Z., et al., Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway. Journal of Biological Chemistry,1998.273(21):p.12901-8.
12. Da Silva, J., et al., Blockade of p38 mitogen-activated protein kinase pathway inhibits inducible nitric-oxide synthase expression in mouse astrocytes. Journal of Biological Chemistry,1997.272(45):p.28373-80.
13. Craxton, A., et al., p38 MAPK is required for CD40-induced gene expression and proliferation in B lymphocytes. Journal of Immunology,1998.161(7):p. 3225-36.
14. Pietersma, A., et al., p38 mitogen activated protein kinase regulates endothelial VCAM-1 expression at the post-transcriptional level. Biochemical and Biophysical Research Communications,1997.230(1):p.44-8.
15. Aihara, Y., et al., Quantitative analysis of gene expressions related to inflammation in canine spastic artery after subarachnoid hemorrhage. Stroke, 2001.32(1):p.212-7.
16. Kubota, T., et al., The kinetics of lymphocyte subsets and macrophages in subarachnoid space after subarachnoid hemorrhage in rats. Stroke,1993. 24(12):p.1993-2000; discussion 2000-1.
17. Sullivan, GW., I.J. Sarembock, and J. Linden, The role of inflammation in vascular diseases. Journal of Leukocyte Biology,2000.67(5):p.591-602.
18. Fassbender, K., et al., Endothelin-1 in subarachnoid hemorrhage:An acute-phase reactant produced by cerebrospinal fluid leukocytes. Stroke,2000. 31(12):p.2971-5.
19. Oshiro, E.M., et al., Inhibition of experimental vasospasm with anti-intercellular adhesion molecule-1 monoclonal antibody in rats. Stroke, 1997.28(10):p.2031-7; discussion 2037-8.
l.Treggiari-Venzi MM, Suter PM, Romand JA.Review of medical prevention of vasospasm after aneurismal subarachnoid hemorrhage:a problem of neurointensive care. Neurosurgery 2001;48:249-261.
2.Cahill J, Calvert JW, Solaroglu I, Zhang JH.Vasospasm and p53-induced apoptosis in an experimental model of subarachnoid hemorrhage. Stroke 2006;37:1868-1874.
3.Zhou C, Yamaguchi M, Kusaka G, Schonholz C, Nanda A, Zhang JH. Caspase inhibitors prevent endothelial apoptosis and cerebral vasospasm in dog model of experimental subarachnoid hemorrhage. J Cereb Blood Flow Metab 2004;24:419-431.
4. Dietrich HH, Dacey Jr RG. Molecular keys to the problems of cerebral vasospasm. Neurosurgery 2000;46:517-30.
5.Varsos VG, Liszczak TM, Han DH, Kistler JP,Vielma J,Black PM,Heros RC,Zervas NT.Delayed cerebral vasospasm is not reversible by aminophylline, nifedipine,or papaverine in a 'two-hemorrhage' canine model. J Neurosurg 1983;58:11-7.
6.Zhen XC,Du W,Romano AG,Friedman E,Harvey JA. The p38 mitogen-activated protein kinase is involved in associative learning in rabbits. J Neuroscience 2001;21:5513-5519.
7.Zhou ML,Shi JX,Zhu JQ,Hang CH,Mao L,Chen KF,Yin HX. Comparison between one- and two-hemorrhage models of cerebral vasospasm in rabbits. J Neurosci Methods 2007; 159:318-324.
8.Chen G, Jiang JY, Shi JX,Ai JL,Hang CH. Effects of recombinant human erythropoietin (rhEPO) on JAK2/STAT3 pathway and endothelial apoptosis in the rabbit basilar artery after subarachnoid hemorrhage. Cytokine 2009;45:162-8.
9.Meguro T, Chen B, Lancon J, Zhang JH. Oxyhemoglobin induces caspase mediated cell death in cerebral endothelial cells. J Neurochem 2001;77:1128-35.
10.Pluta RM, Oldfield EH, Boock RJ. Reversal and prevention of cerebral vasospasm by intracarotid infusions of nitric oxide donors in a primate model of subarachnoid hemorrhage. J Neurosurg 1997;87:746-51.
11.Bombeli T, Karsan A, Tait JF, Harlan JM. Apoptotic vascular endothelial cells become procoagulant. Blood 1997;89:2429-42.
12.Macdonald RL, Weir BK, Runzer TD, Grace MG, Findlay JM, Saito K, Cook DA,Mielke BW,Kanamaru K. Etiology of cerebral vasospasm in primates. J Neurosurg 1991;75:415-24.
13.Clower BR, Yamamoto Y, Cain L, Haines DE, Smith RR. Endothelial injury following experimental subarachnoid hemorrhage in rats:effects on brain blood flow. Anat Rec 1994;240:104-14.
14.Borel CO, McKee A, Parra A, Haglund MM, Solan A, Prabhakar V,Sheng H,Warner DS,Niklason L. Possible role for vascular cell proliferation in cerebral vasospasm after subarachnoid hemorrhage. Stroke 2003;34:427-33.
15.Zarubin T, Han JH. Activation and signaling of the p38 MAP kinase pathway. Cell Research 2005;15:11-18.
16.Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME.Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 1995; 270:1326-31.
17.Juo P, Kuo CJ, Reynolds SE,Konz RF,Raingeaud J,Davis RJ,Biemann HP,Blenis J. Fas activation of the p38 mitogen-activated protein kinase signalling pathway requires ICE/CED-3 family proteases. Mol Cell Biol 1997; 17:24-35.
18.Huang S, Jiang Y, Li Z,Nishida E,Mathias P,Lin S,Ulevitch RJ,Nemerow GR,Han J. Apoptosis signaling pathway in T cells is composed of ICE/Ced-3 family proteases and MAP kinase kinase 6β. Immunity 1997; 6:739-49.
19.Cardone MH, Salvesen GS, Widmann C, Johnson G, Frisch SM.The regulation of anoikis:MEKK-1 activation requires cleavage by caspases. Cell 1997; 90:315-23.
20.Sasaki T,Kasuya H,Onda H,Sasahara A,Goto S,Hori T,Inoue I. Role of p38 mitogen-activated protein kinase on cerebral vasospasm after subarachnoid hemorrhage. Stroke 2004;35; 1466-1470.