缺血预处理对脊髓缺血再灌注损伤保护作用机制的基础研究
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摘要
目的:
研究缺血预处理(ischemic preconditioning,IPC)对缺血再灌注损伤过程中细胞凋亡信号调节激酶-1(apoptosis signal-regulatingkinase 1,ASK1)-丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号转导通路介导的脊髓神经细胞凋亡的影响,并进一步探讨缺血预处理通过调节ASK1和14-3-3的关系从而保护神经细胞的分子生物学机制。
方法:
健康成年新西兰大白兔随机分为空白组(n=5)、缺血再灌注(ischemia reperfusion,IR)组(n=15)、缺血预处理(ischemicpreconditioning,IPC)组(n=15),利用左肾动脉以下腹主动脉阻断法制作脊髓缺血预处理模型和脊髓缺血再灌注损伤模型:空白组实验动物仅麻醉后腹腔切开,无其它特殊处理;IR组实验动物夹闭腹主动脉30min后松开腹主动脉分别再灌注至30min、2h、8h,IPC组先予重复三次短暂缺血5min/再灌注5min预处理后夹闭腹主动脉30min,后松开腹主动脉分别再灌注至30min、2h、8h。背部切口取出L4节段以下脊髓组织。HE染色、电镜检测脊髓神经细胞形态学变化;Western-blot检测脊髓组织中ASK1、c-Jun氨基末端激酶(c-JunN-terminal kinase,JNK)、p38蛋白的表达与活化;免疫共沉淀(immoprecipitation,IP)检测分析ASK1与14-3-3蛋白间的结合与分离。
结果:
形态学观察结果显示:IPC组和再灌注相同时段IR组相比脊髓神经细胞凋亡程度、间质出血程度明显减轻。
Westernblot结果显示:IPC组和再灌注相同时段IR组相比ASK1、JNK、p38蛋白表达程度无明显变化,但活化程度明显降低。
免疫共沉淀结果显示:IPC组和再灌注相同时段IR组相比ASK1和14-3-3蛋白解离程度明显被抑制。
结论:
缺血预处理可减少缺血再灌注损伤过程中脊髓神经细胞的凋亡,而这种抗凋亡作用可能是通过抑制ASK1和14-3-3蛋白的解离进而抑制ASK1及其下游蛋白JNK、p38的活化而介导的。
Objective:
To elucidate the effects of ischemic preconditioning on the apoptosis of neurocytes,ASK1-MAPK signaling cascades and the dissociation of ASK1 from 14-3-3 during reperfusion of ischemic spinal cord.
Methods:
35 Newzealand white rabbits were randomly divided into 3 groups: sham group n=5,in which peritoneotomy was conducted without abdominal aortic cross-clamping(AACC)with arterial clamp;IR group n=15,with 30min in AACC followed by 30min,2h,8h reperfusion;IPC group n=15,with protocol similar to that of IR group except for three-cycle 5 min in IPC prior to AACC.Changes in spinal cord morphology were observed by Hematoxylinand eosin(HE)stain and Electron Microscopy;the activation of ASK1,JNK and p38 was detected by Westernblot;the interaction between ASK1 and 14-3-3 was performed by coimmunoprecipitation analysis.
Results:
No significant changes were observed in sham group.Neurocyte apoptosis was only detected during the 2h and 8h period of reperfusion in IR group while only detected in the 8h period of reperfusion in IPC group. IPC markedly attenuated the ratio of apoptosis caused by reperfusion at the end of reperfusion when compared with IR group.ASK1,JNK and p38 activation was downregulated,and the dissociation of ASK1 from 14-3-3 was inhibited at the same period of reperfusion in IPC group compared to that of IR group(P＜0.05).
Conclusion:
Ischemic preconditioning may inhibit the apoptosis of neurocytes by inhibition of the dissociation of ASK1 from 14-3-3 which induces the activation of ASK1 and its downstreaming signals JNK and p38 during reperfusion of ischemic spinal cord.
研究缺血预处理(ischemic preconditioning,IPC)对缺血再灌注损伤过程中细胞凋亡信号调节激酶-1(apoptosis signal-regulatingkinase 1,ASK1)-丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号转导通路介导的脊髓神经细胞凋亡的影响,并进一步探讨缺血预处理通过调节ASK1和14-3-3的关系从而保护神经细胞的分子生物学机制。
方法:
健康成年新西兰大白兔随机分为空白组(n=5)、缺血再灌注(ischemia reperfusion,IR)组(n=15)、缺血预处理(ischemicpreconditioning,IPC)组(n=15),利用左肾动脉以下腹主动脉阻断法制作脊髓缺血预处理模型和脊髓缺血再灌注损伤模型:空白组实验动物仅麻醉后腹腔切开,无其它特殊处理;IR组实验动物夹闭腹主动脉30min后松开腹主动脉分别再灌注至30min、2h、8h,IPC组先予重复三次短暂缺血5min/再灌注5min预处理后夹闭腹主动脉30min,后松开腹主动脉分别再灌注至30min、2h、8h。背部切口取出L4节段以下脊髓组织。HE染色、电镜检测脊髓神经细胞形态学变化;Western-blot检测脊髓组织中ASK1、c-Jun氨基末端激酶(c-JunN-terminal kinase,JNK)、p38蛋白的表达与活化;免疫共沉淀(immoprecipitation,IP)检测分析ASK1与14-3-3蛋白间的结合与分离。
结果:
形态学观察结果显示:IPC组和再灌注相同时段IR组相比脊髓神经细胞凋亡程度、间质出血程度明显减轻。
Westernblot结果显示:IPC组和再灌注相同时段IR组相比ASK1、JNK、p38蛋白表达程度无明显变化,但活化程度明显降低。
免疫共沉淀结果显示:IPC组和再灌注相同时段IR组相比ASK1和14-3-3蛋白解离程度明显被抑制。
结论:
缺血预处理可减少缺血再灌注损伤过程中脊髓神经细胞的凋亡,而这种抗凋亡作用可能是通过抑制ASK1和14-3-3蛋白的解离进而抑制ASK1及其下游蛋白JNK、p38的活化而介导的。
Objective:
To elucidate the effects of ischemic preconditioning on the apoptosis of neurocytes,ASK1-MAPK signaling cascades and the dissociation of ASK1 from 14-3-3 during reperfusion of ischemic spinal cord.
Methods:
35 Newzealand white rabbits were randomly divided into 3 groups: sham group n=5,in which peritoneotomy was conducted without abdominal aortic cross-clamping(AACC)with arterial clamp;IR group n=15,with 30min in AACC followed by 30min,2h,8h reperfusion;IPC group n=15,with protocol similar to that of IR group except for three-cycle 5 min in IPC prior to AACC.Changes in spinal cord morphology were observed by Hematoxylinand eosin(HE)stain and Electron Microscopy;the activation of ASK1,JNK and p38 was detected by Westernblot;the interaction between ASK1 and 14-3-3 was performed by coimmunoprecipitation analysis.
Results:
No significant changes were observed in sham group.Neurocyte apoptosis was only detected during the 2h and 8h period of reperfusion in IR group while only detected in the 8h period of reperfusion in IPC group. IPC markedly attenuated the ratio of apoptosis caused by reperfusion at the end of reperfusion when compared with IR group.ASK1,JNK and p38 activation was downregulated,and the dissociation of ASK1 from 14-3-3 was inhibited at the same period of reperfusion in IPC group compared to that of IR group(P＜0.05).
Conclusion:
Ischemic preconditioning may inhibit the apoptosis of neurocytes by inhibition of the dissociation of ASK1 from 14-3-3 which induces the activation of ASK1 and its downstreaming signals JNK and p38 during reperfusion of ischemic spinal cord.
引文
[1] Murry CE, Jennings RB, Reimer KA,Preconditioning with ischemia: a delay of lethal injury in ischemic myocardium,Circulation. 74 (1986)1124-1136
[2] Schoen M, Rotter R, Gierer P, Gradl G, Strauss U, Jonas L, Mittlmeier T, Vollmar B,Ischemic preconditioning prevents skeletal muscle tissue injury, but not nerve lesion upon tourniquet-induced ischemia,J Trauma. 63(2007)788-797
[3] Choi YS, Cho KO, Kim EJ, Sung KW, Kim SY,Ischemic preconditioning in the rat hippocampus increases antioxidant activities but does not affect the level of hydroxyl radicals during subsequent severe ischemia, Exp Mol Med.39(2007)556-563
[4] Yamada F, Saito T, Abe T, Tsuchiya T, Sato Y, Kenjo A, Kimura T, Gotoh M,Ischemic preconditioning enhances regenerative capacity of hepatocytes in long-term ischemically damaged rat livers, J Gastroenterol Hepatol. 22(2007)1971-1977
[5] Obolensky A, Berenshtein E, Konijn AM, Banin E, Chevion M,Ischemic preconditioning of the rat retina: Protective role of ferritin,Free Radic Biol Med. 2007 [Epub ahead of print]
[6] Ferencz A, Racz B, Gasz B, Benko L, Jancso G, Kurthy M, Roth E,Intestinal ischemic preconditioning in rats and NF-kappaB activation,Microsurgery. 26(2006) 54-57
[7] Meiko Kakimoto, Masahiko Kawaguchi, Takanori Sakamoto, Evaluation of Rapid Ischemic Preconditioning in a RabbitModel of Spinal Cord Ischemia,Anesthesiology. 99(2003)1112-1127
[8] Matejikova J, Kucharska J, Pinterova M, Pancza D, Ravingerova T,Protection against ischaemia-induced ventricular arrhythmias and myocardial dysfunction conferred by preconditioning in the rat heart: Involvement of mitochondrial K(ATP) channels and reactive oxygen species,Physiol Res. 2008 Jan 17; [Epub ahead of print]
[9] Kuno A, Critz SD, Cui L, Solodushko V, Yang XM, Krahn T, Albrecht B, Philipp S, Cohen MV, Downey JM,Protein kinase C protects preconditioned rabbit hearts by increasing sensitivity of adenosine A2b-dependent signaling during early reperfusion, J Mol Cell Cardiol.43(2007)262-271. Epub 2007 May 24.
[10] Yang B, Harris KP, Jain S, Nicholson ML,Caspase-7, Fas and FasL in long-term renal ischaemia/reperfusion and immunosuppressive injuries in rats,Am J Nephrol. 27(2007) 397-408. Epub 2007 Jun 26
[11] Peng Wang, Xiaojian Cao, David J. Nagel, Guoyong Yin,Activation of ASK1 during reperfusion of ischemic spinal cord,Neurosci Lett. 415(2007)248-252.
[12] H. Ichijo, E. Nishida, K. Irie, P. ten Dijke, M. Saitoh, T. Moriguchi, M.Takagi, K. Matsumoto, K. Miyazono, Y. Gotoh, Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways, Science 275 (1997) 90-94.
[13]H.Y. Chang, H. Nishitoh, X. Yang, H. Ichijo, D. Baltimore, Activation of apoptosis signal-regulating kinase 1 (ASKl) by the adapter protein Daxx,Science 281 (1998) 1860-1863.
[14] Y. Gotoh, J.A. Cooper, Reactive oxygen species- and dimerization-induced activation of apoptosis signal-regulating kinase 1 in tumor necrosis factoralpha signal transduction, J. Biol. Chem. 273 (1998) 17477-17482.
[15] Matsuzawa, H. Ichijo, Stress-responsive protein kinases in redoxregulated apoptosis signaling, Antioxid. Redox Signal. 7 (2005) 472-481.
[16] E.H. Goldman, L. Chen, H. Fu, Activation of apoptosis signal-regulating kinase 1 by reactive oxygen species through dephosphorylation at serine 967 and 14-3-3 dissociation, J. Biol. Chem. 279 (2004) 10442-10449.
[17] S. Nakahara, K. Yone, T. Sakou, S. Wada, T. Nagamine, T. Niiyama, H.Ichijo, Induction of apoptosis signal regulating kinase 1 (ASK1) after spinal cord injury in rats: possible involvement of ASKl-JNK and -p38 pathways in neuronal apoptosis, J. Neuropathol. Exp. Neurol. 58 (1999) 442-450.
[18] Fan T, Wang CC,Wang FM,et al.Experimental study of the protection of ischemic preconditioning to spinal cord ischemia.Surg Neurol. 52(1999):299-305.
[19] Ondrejcak T,Vanicky I.Jacobs MJ,et al.Ischemic preconditioning does not improve neurological recovery after spinal cord compression injury in the rat.Brain Res. 995(2004):267-273
[20] Li YZ, Liu XH, Zhu XM, Cai LR.ARC contributes to the inhibitory effect of preconditioning on cardiomyocyte apoptosis.Apoptosis. 12(2007):1589-95.
[21] Quireze C, Montero EF, Leitao RM, Juliano Y, Fagundes DJ, preconditioning prevents apoptotic cell death and necrosis in early and intermediate phases of liver ischemia-reperfusion injury in rats.J Invest Surg. 19(2006):229-36.
[22] Liu Y, Sercombe R, Xie D, Liu K, Chen L.Inhibition of caspase-9 activation an involved in ischemic preconditioning-induced neuroprotection in rat brain.Neurol Res.2007 [Epub ahead of print]
[23] Choi YS,Cho K0,Kim EJ,et al. Ischemic preconditioning in the rat hippocampus increases antioxidant activities but does not affect the level of hydroxyl radicals during subsequent severe ischemia.Exp Mol Med. 39(2007):556-63.
[24] Lazou A,Iliodromitis EK,Cieslak D,et al.Ischemic but not mechanical preconditioning attenuates ischemia/reperfusion induced myocardial apoptosis in anaesthetized rabbits: the role of Bcl-2 family proteins and ERK1/2.Apoptosis.11(2006):2195-204.
[25] Takeda K,Matsuzawa A,Nishitoh H,et al. Roles of MAPKKK ASK1 in stress-induced cell death. Cell Struct Funct. 28(2003):23-29.
[26] Morita K,Saitoh M,Tobiume K,et al.Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress. Embo J. 20(2001):6028-6036.
[27]Nishitoh H,Saitoh M,Mochida Y,et al.ASK1 is essential for JNK/SAPK activation by TRAF2. Mol Cell.2(1998):389-395.
[28] Liu Y,Yin G, Surapisitchat J,et al.Laminar flow inhibits TNF-induced ASK1 activation by preventing dissociation of ASK1 from its inhibitor 14-3-3. J Clin Invest. 107 (2001):917-923.
[29] Goldman EH,Chen L,Fu H.Activation of apoptosis signal-regulating kinase 1 by reactive oxygen species through dephosphorylation at serine 967 and 14-3-3 dissociation. J Biol Chem. 279(2004):10442-10449.
[30] Subramanian RR,Zhang H,Wang H,et al. Interaction of apoptosis signal-regulating kinase 1 with isoforms of 14-3-3 proteins. Exp Cell Res. 294(2004):581-591.
[31] Liu G,Rondinone CM. JNK:bridging the insulin signaling and inflammatory pathway.Curr Opin Investig Drugs. 10(2005):979-87.
[32] Enslen H,Brancho DM,Davis RJ.Molecular determinants that mediate selective activation of p38 MAP kinase isoforms.Embo J.19(2000):1301-11.
[1] McCully JD, Toyoda Y, Uematsu M, et al.Adenosine enhanced ischemic preconditioning:adenosine receptor involvement during ischemia and reperfusion. Am J Physiol Heart Circ Physiol, 2001,280:H591—602.
[2] Wang GY, Wu S, Pei JM, et al. Kappa but not delta-opioid receptors mediate effects of ischemic preconditioning on both infarct and arrhthmia in rats. Am J Physiol Heart Circ Physiol, 2001 280:H384-391.
[3] Schulz R, Post H, Vahlhaus C,et al. Ischemic preconditioning in pigs; a graded phnomenon; its relation to adenosine and bra-dykinin. Circulation, 1998, 98 :1022-1029.
[4] TannoM ,Tsuchida A ,NozawaY ,e ta l.Roles of tyrosine kinase and protein kinase C in infarct size limitation by repetitive ischemic preconditioning in the rat.J Cardiovasc Pharmacol,2000,35:345-352.
[5] Tang XL,Kodani E ,Takano H ,et al.Protein tyrosine kinase signaling is necessary for NO donor-induced late preconditioning against myocardial stunning. A m J Physiol Heart Circ Physiol,2003, 284:H1441-H1448.
[6] Nishida M,Maruyama Y,Tanaka R,et al.G alpha(i) and G alpha(o),target proteins of reactive oxygen species. Nature,2000,4 08:492-495.
[7] Agnes H,Nagy L,Parratt JR,et al.N-2-mercaptopropionylglycine,a scavenger of reactive oxygen species,does not modify the early antiarrhythmic effect of ischaemic preconditioning in anaesthetized dogs. Car-dopvasc Drugs Ther,2004,18449-459.
[8] Cain BS,Meldrum DR,Clevland JC Jr,et al. Clinical I-type Ca(2+) channel blockade prevents ischemic preconditioning of human myocardium.J Mol Cell Cardiol,20 00,31:2191-2197.
[9] Sanada S, Kitakaze M, Asanuma H, et al.Role of mitochondrial and sarcolemmal K(ATP ) channels in ischemic preconditioning Of the canine heart.Am J Physiol Heart Circ Physiol, 2001,280:H256-263.
[10] Downey JM,Cohen MV. Mitochondrial K(ATP ) channel opening during index ischemia and following myocardial reperfusion in ischemic rat hearts.J Mol Cell Cardiol,2001,33: 651-665.
[11] Valtchanova-Mathcouganska A,Gondwe M, Nadar A.C-reactive protein in acute and delayed preconditioning of the rat heart. Cardiovasc J S Afr, 2005,16:118-123.
[12] Hoshida S, Yamashita N, Otsu K, et al.Repeated physiologic stresses provide persistent cardioprotection against ischemia reperfusion injury in rats. J Am Coll Cardiol,2002, 40:826-831.
[13] Tang XL,Takano H,Rizvi A,et al.Oxidant species trigger late preconditioning against myocardial stunning in conscious rabbits.Am J Physiol heart Circ Physiol,2002,282:H281-H291.
[14]Takano H ,Bolli R,Black RG Jr,et al.A(1) or A(3) adenosine receptors induce late preconditioning against infarction in conscious rabbits by different mechanisms.Cire Res, 2001,88:520-528.
[15] Xuan YT,Guo Y, Zhu Y, et al.Mechanism of cyclooxygenase-2 upregulation in late preconditioning. J Mol Cel Cardiol,2003, 35:525-537.
[16] Malhotra S, Savitz SI, Ocava L, et al. Ischemic preconditioning is mediated by erythropoietin through PI-3 kinase signaling in an animal model of transient ischemic attack. J Neurosci Res, 2005,104:1762-1768.
[17] Xuan YT,Tang XL,Qiu Y,et al.Biphasic response of cardiac NO synthase isoforms to ischemic preconditioning in conscious rabbits.Am J Physiol Heat Circ Physiol,2000, 279:H2360-H2371.
[18] Shinmura K,Xuan YT,Tang XL,et al.Inducible nitric oxide synthase modulates cyclooxygenase-2 activity in the heart of conscious rabbits during the late phase of iscbemic preconditioning. Circ Res,2002,90:602-608.
[19] Mcleod CJ, Hoyt RF Jr, Sack MN. UCP-2, a functional target in delayed preconditioning induced cardioprotection? Cardiovase J S Afr,2004,15:4-8.
[20] Peralta C, Fernandez L, Panes J, et al.Preconditioning protects against systemic disorders associated with hepatic ischemia reperfusion through blockade of tumor necrosis factor-induced P-selectin upregulation in the rat. Hepatology, 2001,33:100-113.
[21]Harkin DW, Barros D Sa AA, McCallion K,et al.Ischemic preconditioning before lower limb ischemia-reperfusion protects against acute lung injury. J Vase Surg,2002,35:1264-1273.
[22] Kharbanda RK,Peters M,Walton B,et al.Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo. Circulation, 2001,103: 1624-1630.
[23] Dong JH,Liu YX,Ji ES,et al.Limb ischemic preconditioning reduces infarct size following myocardial ischemia reperfusion in rats. Sheng Li Xue Bao, 2004,25:41-46.
[24] Moses MA, Addison PD, Neligan PC, et al. Mitochondrial KATP channels in hindlimb remote ischemic preconditioning of skeletal muscle against infarction. Am J Physiol Heart Circ Physiol, 2005,288:H559-567.
[25] Moses MA,Addison PD,Neligan PC,et al.Inducing late phase of infarct protection in skeletal muscle by remote preconditioning: efficacy and mechanism.Am J Physiol Regul Integr Comp Physiol, 2005,289:R1609-1617.
[26] Cave AC,Collis CS,Downey JM,et al.Improved functional recovery by ischaemic preconditioning is not mediated by adenosione in the globally ischaemic isolated rat heart.Cardio vasc Res, 1993,27: 663-668.
[27] Liu Y,Ytrehus K,Downey JM.Evidence that translocation of protein kinase C is a key event during ischemic preconditioning of rabbit myocardium.J Mol Cell Cardiol,1994,26:661-668.
[28] Yao Z,Gross GJ.Role of nitric oxide,muscarinic receptors,and the ATP-sensitive K~+ channel in mediating the effects of acetylcholine to mimic preconditioing in dogs.Circ Res,1993,73:1193-1201.
[2] Schoen M, Rotter R, Gierer P, Gradl G, Strauss U, Jonas L, Mittlmeier T, Vollmar B,Ischemic preconditioning prevents skeletal muscle tissue injury, but not nerve lesion upon tourniquet-induced ischemia,J Trauma. 63(2007)788-797
[3] Choi YS, Cho KO, Kim EJ, Sung KW, Kim SY,Ischemic preconditioning in the rat hippocampus increases antioxidant activities but does not affect the level of hydroxyl radicals during subsequent severe ischemia, Exp Mol Med.39(2007)556-563
[4] Yamada F, Saito T, Abe T, Tsuchiya T, Sato Y, Kenjo A, Kimura T, Gotoh M,Ischemic preconditioning enhances regenerative capacity of hepatocytes in long-term ischemically damaged rat livers, J Gastroenterol Hepatol. 22(2007)1971-1977
[5] Obolensky A, Berenshtein E, Konijn AM, Banin E, Chevion M,Ischemic preconditioning of the rat retina: Protective role of ferritin,Free Radic Biol Med. 2007 [Epub ahead of print]
[6] Ferencz A, Racz B, Gasz B, Benko L, Jancso G, Kurthy M, Roth E,Intestinal ischemic preconditioning in rats and NF-kappaB activation,Microsurgery. 26(2006) 54-57
[7] Meiko Kakimoto, Masahiko Kawaguchi, Takanori Sakamoto, Evaluation of Rapid Ischemic Preconditioning in a RabbitModel of Spinal Cord Ischemia,Anesthesiology. 99(2003)1112-1127
[8] Matejikova J, Kucharska J, Pinterova M, Pancza D, Ravingerova T,Protection against ischaemia-induced ventricular arrhythmias and myocardial dysfunction conferred by preconditioning in the rat heart: Involvement of mitochondrial K(ATP) channels and reactive oxygen species,Physiol Res. 2008 Jan 17; [Epub ahead of print]
[9] Kuno A, Critz SD, Cui L, Solodushko V, Yang XM, Krahn T, Albrecht B, Philipp S, Cohen MV, Downey JM,Protein kinase C protects preconditioned rabbit hearts by increasing sensitivity of adenosine A2b-dependent signaling during early reperfusion, J Mol Cell Cardiol.43(2007)262-271. Epub 2007 May 24.
[10] Yang B, Harris KP, Jain S, Nicholson ML,Caspase-7, Fas and FasL in long-term renal ischaemia/reperfusion and immunosuppressive injuries in rats,Am J Nephrol. 27(2007) 397-408. Epub 2007 Jun 26
[11] Peng Wang, Xiaojian Cao, David J. Nagel, Guoyong Yin,Activation of ASK1 during reperfusion of ischemic spinal cord,Neurosci Lett. 415(2007)248-252.
[12] H. Ichijo, E. Nishida, K. Irie, P. ten Dijke, M. Saitoh, T. Moriguchi, M.Takagi, K. Matsumoto, K. Miyazono, Y. Gotoh, Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways, Science 275 (1997) 90-94.
[13]H.Y. Chang, H. Nishitoh, X. Yang, H. Ichijo, D. Baltimore, Activation of apoptosis signal-regulating kinase 1 (ASKl) by the adapter protein Daxx,Science 281 (1998) 1860-1863.
[14] Y. Gotoh, J.A. Cooper, Reactive oxygen species- and dimerization-induced activation of apoptosis signal-regulating kinase 1 in tumor necrosis factoralpha signal transduction, J. Biol. Chem. 273 (1998) 17477-17482.
[15] Matsuzawa, H. Ichijo, Stress-responsive protein kinases in redoxregulated apoptosis signaling, Antioxid. Redox Signal. 7 (2005) 472-481.
[16] E.H. Goldman, L. Chen, H. Fu, Activation of apoptosis signal-regulating kinase 1 by reactive oxygen species through dephosphorylation at serine 967 and 14-3-3 dissociation, J. Biol. Chem. 279 (2004) 10442-10449.
[17] S. Nakahara, K. Yone, T. Sakou, S. Wada, T. Nagamine, T. Niiyama, H.Ichijo, Induction of apoptosis signal regulating kinase 1 (ASK1) after spinal cord injury in rats: possible involvement of ASKl-JNK and -p38 pathways in neuronal apoptosis, J. Neuropathol. Exp. Neurol. 58 (1999) 442-450.
[18] Fan T, Wang CC,Wang FM,et al.Experimental study of the protection of ischemic preconditioning to spinal cord ischemia.Surg Neurol. 52(1999):299-305.
[19] Ondrejcak T,Vanicky I.Jacobs MJ,et al.Ischemic preconditioning does not improve neurological recovery after spinal cord compression injury in the rat.Brain Res. 995(2004):267-273
[20] Li YZ, Liu XH, Zhu XM, Cai LR.ARC contributes to the inhibitory effect of preconditioning on cardiomyocyte apoptosis.Apoptosis. 12(2007):1589-95.
[21] Quireze C, Montero EF, Leitao RM, Juliano Y, Fagundes DJ, preconditioning prevents apoptotic cell death and necrosis in early and intermediate phases of liver ischemia-reperfusion injury in rats.J Invest Surg. 19(2006):229-36.
[22] Liu Y, Sercombe R, Xie D, Liu K, Chen L.Inhibition of caspase-9 activation an involved in ischemic preconditioning-induced neuroprotection in rat brain.Neurol Res.2007 [Epub ahead of print]
[23] Choi YS,Cho K0,Kim EJ,et al. Ischemic preconditioning in the rat hippocampus increases antioxidant activities but does not affect the level of hydroxyl radicals during subsequent severe ischemia.Exp Mol Med. 39(2007):556-63.
[24] Lazou A,Iliodromitis EK,Cieslak D,et al.Ischemic but not mechanical preconditioning attenuates ischemia/reperfusion induced myocardial apoptosis in anaesthetized rabbits: the role of Bcl-2 family proteins and ERK1/2.Apoptosis.11(2006):2195-204.
[25] Takeda K,Matsuzawa A,Nishitoh H,et al. Roles of MAPKKK ASK1 in stress-induced cell death. Cell Struct Funct. 28(2003):23-29.
[26] Morita K,Saitoh M,Tobiume K,et al.Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress. Embo J. 20(2001):6028-6036.
[27]Nishitoh H,Saitoh M,Mochida Y,et al.ASK1 is essential for JNK/SAPK activation by TRAF2. Mol Cell.2(1998):389-395.
[28] Liu Y,Yin G, Surapisitchat J,et al.Laminar flow inhibits TNF-induced ASK1 activation by preventing dissociation of ASK1 from its inhibitor 14-3-3. J Clin Invest. 107 (2001):917-923.
[29] Goldman EH,Chen L,Fu H.Activation of apoptosis signal-regulating kinase 1 by reactive oxygen species through dephosphorylation at serine 967 and 14-3-3 dissociation. J Biol Chem. 279(2004):10442-10449.
[30] Subramanian RR,Zhang H,Wang H,et al. Interaction of apoptosis signal-regulating kinase 1 with isoforms of 14-3-3 proteins. Exp Cell Res. 294(2004):581-591.
[31] Liu G,Rondinone CM. JNK:bridging the insulin signaling and inflammatory pathway.Curr Opin Investig Drugs. 10(2005):979-87.
[32] Enslen H,Brancho DM,Davis RJ.Molecular determinants that mediate selective activation of p38 MAP kinase isoforms.Embo J.19(2000):1301-11.
[1] McCully JD, Toyoda Y, Uematsu M, et al.Adenosine enhanced ischemic preconditioning:adenosine receptor involvement during ischemia and reperfusion. Am J Physiol Heart Circ Physiol, 2001,280:H591—602.
[2] Wang GY, Wu S, Pei JM, et al. Kappa but not delta-opioid receptors mediate effects of ischemic preconditioning on both infarct and arrhthmia in rats. Am J Physiol Heart Circ Physiol, 2001 280:H384-391.
[3] Schulz R, Post H, Vahlhaus C,et al. Ischemic preconditioning in pigs; a graded phnomenon; its relation to adenosine and bra-dykinin. Circulation, 1998, 98 :1022-1029.
[4] TannoM ,Tsuchida A ,NozawaY ,e ta l.Roles of tyrosine kinase and protein kinase C in infarct size limitation by repetitive ischemic preconditioning in the rat.J Cardiovasc Pharmacol,2000,35:345-352.
[5] Tang XL,Kodani E ,Takano H ,et al.Protein tyrosine kinase signaling is necessary for NO donor-induced late preconditioning against myocardial stunning. A m J Physiol Heart Circ Physiol,2003, 284:H1441-H1448.
[6] Nishida M,Maruyama Y,Tanaka R,et al.G alpha(i) and G alpha(o),target proteins of reactive oxygen species. Nature,2000,4 08:492-495.
[7] Agnes H,Nagy L,Parratt JR,et al.N-2-mercaptopropionylglycine,a scavenger of reactive oxygen species,does not modify the early antiarrhythmic effect of ischaemic preconditioning in anaesthetized dogs. Car-dopvasc Drugs Ther,2004,18449-459.
[8] Cain BS,Meldrum DR,Clevland JC Jr,et al. Clinical I-type Ca(2+) channel blockade prevents ischemic preconditioning of human myocardium.J Mol Cell Cardiol,20 00,31:2191-2197.
[9] Sanada S, Kitakaze M, Asanuma H, et al.Role of mitochondrial and sarcolemmal K(ATP ) channels in ischemic preconditioning Of the canine heart.Am J Physiol Heart Circ Physiol, 2001,280:H256-263.
[10] Downey JM,Cohen MV. Mitochondrial K(ATP ) channel opening during index ischemia and following myocardial reperfusion in ischemic rat hearts.J Mol Cell Cardiol,2001,33: 651-665.
[11] Valtchanova-Mathcouganska A,Gondwe M, Nadar A.C-reactive protein in acute and delayed preconditioning of the rat heart. Cardiovasc J S Afr, 2005,16:118-123.
[12] Hoshida S, Yamashita N, Otsu K, et al.Repeated physiologic stresses provide persistent cardioprotection against ischemia reperfusion injury in rats. J Am Coll Cardiol,2002, 40:826-831.
[13] Tang XL,Takano H,Rizvi A,et al.Oxidant species trigger late preconditioning against myocardial stunning in conscious rabbits.Am J Physiol heart Circ Physiol,2002,282:H281-H291.
[14]Takano H ,Bolli R,Black RG Jr,et al.A(1) or A(3) adenosine receptors induce late preconditioning against infarction in conscious rabbits by different mechanisms.Cire Res, 2001,88:520-528.
[15] Xuan YT,Guo Y, Zhu Y, et al.Mechanism of cyclooxygenase-2 upregulation in late preconditioning. J Mol Cel Cardiol,2003, 35:525-537.
[16] Malhotra S, Savitz SI, Ocava L, et al. Ischemic preconditioning is mediated by erythropoietin through PI-3 kinase signaling in an animal model of transient ischemic attack. J Neurosci Res, 2005,104:1762-1768.
[17] Xuan YT,Tang XL,Qiu Y,et al.Biphasic response of cardiac NO synthase isoforms to ischemic preconditioning in conscious rabbits.Am J Physiol Heat Circ Physiol,2000, 279:H2360-H2371.
[18] Shinmura K,Xuan YT,Tang XL,et al.Inducible nitric oxide synthase modulates cyclooxygenase-2 activity in the heart of conscious rabbits during the late phase of iscbemic preconditioning. Circ Res,2002,90:602-608.
[19] Mcleod CJ, Hoyt RF Jr, Sack MN. UCP-2, a functional target in delayed preconditioning induced cardioprotection? Cardiovase J S Afr,2004,15:4-8.
[20] Peralta C, Fernandez L, Panes J, et al.Preconditioning protects against systemic disorders associated with hepatic ischemia reperfusion through blockade of tumor necrosis factor-induced P-selectin upregulation in the rat. Hepatology, 2001,33:100-113.
[21]Harkin DW, Barros D Sa AA, McCallion K,et al.Ischemic preconditioning before lower limb ischemia-reperfusion protects against acute lung injury. J Vase Surg,2002,35:1264-1273.
[22] Kharbanda RK,Peters M,Walton B,et al.Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivo. Circulation, 2001,103: 1624-1630.
[23] Dong JH,Liu YX,Ji ES,et al.Limb ischemic preconditioning reduces infarct size following myocardial ischemia reperfusion in rats. Sheng Li Xue Bao, 2004,25:41-46.
[24] Moses MA, Addison PD, Neligan PC, et al. Mitochondrial KATP channels in hindlimb remote ischemic preconditioning of skeletal muscle against infarction. Am J Physiol Heart Circ Physiol, 2005,288:H559-567.
[25] Moses MA,Addison PD,Neligan PC,et al.Inducing late phase of infarct protection in skeletal muscle by remote preconditioning: efficacy and mechanism.Am J Physiol Regul Integr Comp Physiol, 2005,289:R1609-1617.
[26] Cave AC,Collis CS,Downey JM,et al.Improved functional recovery by ischaemic preconditioning is not mediated by adenosione in the globally ischaemic isolated rat heart.Cardio vasc Res, 1993,27: 663-668.
[27] Liu Y,Ytrehus K,Downey JM.Evidence that translocation of protein kinase C is a key event during ischemic preconditioning of rabbit myocardium.J Mol Cell Cardiol,1994,26:661-668.
[28] Yao Z,Gross GJ.Role of nitric oxide,muscarinic receptors,and the ATP-sensitive K~+ channel in mediating the effects of acetylcholine to mimic preconditioing in dogs.Circ Res,1993,73:1193-1201.