NMDA受体激活在急性肺损伤CCTα表达下调中的作用及机制
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摘要
第一章MK801对小鼠油酸型肺损伤的保护作用
研究背景急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)是临床常见危重疾病,发病机制尚未完全阐明。肺内中性粒细胞、巨噬细胞的滞留和激活在ARDS的发生发展中起重要作用。中性粒细胞、巨噬细胞可释放谷氨酸。Said等人发现谷氨酸离子型受体特异性激动剂N-甲基-D-门冬氨酸(N-methyl-D-aspartate,NMDA)可引起离体灌流肺发生高通透性肺水肿。近年来本室的研究还发现NMDA受体阻断剂MK-801对脂多糖(Lipopolysaccharide,LPS)和高氧等引起的肺损伤具有明显的保护作用,这些研究进一步提示内源性谷氨酸(Glutamate,Glu)的大量释放过度激活NMDA受体参与急性肺损伤的发生发展过程。但为证明内源性Glu的大量释放过度激活NMDA受体在急性肺损伤的发生中具有普遍意义,尚有待在不同模型上进一步证实。
方法(1)建立小鼠急性油酸肺损伤模型;(2)测量肺湿重和干重的比值(W/D)并观察肺组织病理变化,以反映肺组织的损伤程度;(3)测定支气管肺泡灌洗液中蛋白和白细胞含量,以反映支气管肺泡毛细血管通透性变化;(4)生化测定肺组织髓过氧化物酶(MPO),反映氧化损伤时的肺炎性改变;(5)RT-PCR和免疫组化分别检测CTP:磷酸胆碱二胞苷酰基转移酶α(CTP:phosphocholinecytidylyltransferase alpha,CCTα)mRNA和蛋白水平,反映CCTα转录合成的变化。
结果油酸(0.1 ml/kg)尾静脉注射4 h可引起肺组织肺指数、肺湿干重比W/D增加、肺组织MPO活性增加,支气管肺泡灌洗液中蛋白和白细胞含量明显增加,并引起肺组织CCTαmRNA和蛋白水平的明显减低,病理切片示水肿、炎症渗出明显。NMDA受体的阻断剂MK-801(0.1mg/kg,ip)预处理30 min可减轻油酸引起的上述变化。
结论油酸引起明显以炎性渗出为主的急性肺损伤,肺内NMDA受体的激活参与油酸急性肺损伤的发生,并引起CCTα表达的下调。
第二章NMDA抑制CCTα表达的转录调控机制
研究背景CTP:磷酸胆碱二胞苷酰基转移酶(CTP:phosphocholinecytidylyltransferase alpha,CCTα)是磷脂酰胆碱(phosphatidylcholine,PC)合成中的关键调控酶。CCTα基因近端启动子区包含多个与细胞生长、分化密切相关的转录因子Sp1(specificity protein 1)结合位点。探讨Sp1在CCTα启动转录中的作用具有一定的意义。在急性肺损伤(acute lung iniury,ALI)及ARDS等肺部损伤疾病中,肺表面活性物质(pulmonary surfactant,PS)系统功能的异常并参与肺损伤的发生过程。本室前期研究证明一定剂量NMDA作用后,肺Ⅱ型上皮细胞合成CCT mRNA水平、CCTα蛋白表达水平均下降。本研究旨在观察NMDA受体激活后Sp1的改变,探讨NMDA抑制CCTα表达的分子机制。
方法(1)萤光素酶报告基因活性检测CCTα启动子活性;(2)荧光定量PCR定量检测Sp1表达质粒后CCTαmRNA;(3)Western blot检测A549细胞转染Sp1表达质粒后CCTα蛋白含量表达水平;(4)Western blot检测A549细胞经NMDA处理后Sp1蛋白含量表达水平;(5)荧光定量PCR定量检测A549细胞经NMDA处理后Sp1mRNA水平;(6)EMSA检测CCTα启动子上Sp1的DNA结合活性及NMDA处理对其影响。
结果转染Sp1真核表达质粒30 h后,A549细胞CCTα核心启动子报告基因相对萤光素酶活性增加,A549细胞CCTαm RNA表达水平表达水平增高。转染Sp1真核表达质粒36 h后,CCTα蛋白表达水平表达水平增高。A549细胞经NMDA处理8 h后,Sp1蛋白表达明显下降,并呈时间、剂量依赖。Sp1 mRNA水平没有明显的改变。EMSA检测显示,NMDA处理后A549细胞的核蛋白中转录因子Sp1与DNA的结合活性下调。
结论转录因子Sp1促进A549细胞CCTα的启动子活性,增加CCTα的合成表达。NMDA通过下调核内Sp1蛋白与DNA结合活性而抑制CCTα的表达。
Chapter 1 Effect of MK-801 on oleic acid-induced acute lung injury in mice
Background Acute respiratory distress syndrome(ARDS)is a common clinical syndrome.The exact pathogenesis of ARDS,however, is not well characterized.Pulmonary neutrophil sequestration and the activation of neutrophils and alveolar macrophages play key roles in the pathogenesis of ARDS.It has been shown that glutamate released from activated neutrophils acts as a source of excitotoxic injury of other cells. Both macrophages and activated neutrophils release glutamate.Said et al.reported that administration of high concentrations of glutamate or glutamate agonist NMDA can elicit an acute,high-permeability pulmonary edema.In recent years,we find that the NMDA receptor antagonist MK-801(dizocilpine)attenuates lipopolysaccharide(LPS) and hyperoxia-induced lung injury.These findings suggested that lung injury(caused by LPS and hyperoxia)could be mediated partly by endogenous glutamate release and toxic overactivation of NMDA receptors.Therefore,glutamate receptors may serve novel,yet to-be characterized injury factor during acute lung injury.Further studies in different animal models of lung injury are required before assuming their universal significance.
Methods(1)Oleic acid(0.1ml/kg)was injected via the caudal vein to induce acute lung injury model in mice.(2)Lung wet-to-dry weight ratio (W/D)and histopathological examination were used to evaluate the severity of pulmonary edema.(3)Lung tissue myeloperoxidase(MPO) activity was quantified by using commercial kits as a reflection of neutrophil sequestration.(4)Total neutrophil count and total protein concentration in bronchoalveolar lavage fluid(BALF)were determined to reflect changes in alveolar-capillary permeability.(5)The mRNA level of CCTαin the lung was measured by RT-PCR,and the expression of CCTαprotein was semi-quantified by immunohistochemistry.
Results(1)Oleic acid-induced increases in the concentration of total protein and the numbers of neutrophils in BALF were significantly attenuated in MK-801(0.1mg/kg,ip)pretreated mice;(2)MK-801 pretreatment also resulted in a significant protection in lung tissue tested against oleic acid-induced acute lung injury via decreasing W/D ratio, MPO activity.(3)The CCTαexpression decreased in oleic acid-induced lung injury model,both at protein and mRNA levels. MK-801 pretreatment attenuated oleic acid-induced down-regulation of CCTαexpression in the lung.
Conclusion Oleic acid caused an acute lung damage characterized by severe edema formation and pulmonary inflammation in mice. Endogenous NMDA receptor activation may play an important role in mediating oleic acid-induced lung injury.In this model,expression of CCTαwas decreased.
Chapter 2 Study on the transcriptional regulation mechanism of CTP:phosphocholine cytidylyltransferase alpha expression inhibition by NMDA
Background CTP:phosphocholinecytidylyltransferase alpha(CCTα) is the major rate-limiting enzyme for phosphatidylcholine(PC)synthesis. The promoter of CCTαis GC rich,and contains several binding sites for the specificity protein 1(Sp1)transcription factor,which is thought to play an important role in regulating cell growth and differentiation.The dysfunction of pulmonary surfactant(PS)is thought to be a important factor during the development of acute lung injury(including ARDS). Previous work in our group has demonstrated NMDA can repress CCTαmRNA and protein expression in pulmonary alveolar typeⅡcells.In this study,we examined the changes in Sp1 expression after NMDA treatment and the molecular mechanism of transcriptional regulation of inhibition of CCTαexpression by NMDA.
Methods(1)CCTαpromotor activity was measured using Dual-luciferase reporter assay system.(2)CCTαmRNA expression was measured by RT-PCR after 30 h of transfection with Sp1(pEVR2-Sp1) expression plasmid.(3)CCTαprotein level was measured by Western blot after 36 h of transfection with pEVR2-Sp1 plasmid.(4)Sp1 protein in nuclear extracts after NMDA treatment was measured by Western blot.Sp1 mRNA was measured by RT-PCR,and Sp1 DNA binding activity was measured by EMSA.
Results Transfection of the A549 cells with the Sp1 expression plasmid,pEVR2-Sp1,resulted in an increase in promoter activity,and as well as increases in CCTαmRNA and protein.Treatment of A549 cells with NMDA for 8h,the level of Sp1 protein decreased in a dose- and time-dependent manner in nuclear protein.But the level of Sp1 mRNA did not change significantly.EMSA showed that NMDA inhibited the DNA binding activity of Splin A549 cells.
Conclusion Sp1 promotes the CCTαpromoter acticity and increase expression of CCTαin A549 cells.NMDA receptor activation inhibites CCTαexpression by decreaseing Sp1 protein and DNA binding activity in neuclear of A549 cells.
研究背景急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)是临床常见危重疾病,发病机制尚未完全阐明。肺内中性粒细胞、巨噬细胞的滞留和激活在ARDS的发生发展中起重要作用。中性粒细胞、巨噬细胞可释放谷氨酸。Said等人发现谷氨酸离子型受体特异性激动剂N-甲基-D-门冬氨酸(N-methyl-D-aspartate,NMDA)可引起离体灌流肺发生高通透性肺水肿。近年来本室的研究还发现NMDA受体阻断剂MK-801对脂多糖(Lipopolysaccharide,LPS)和高氧等引起的肺损伤具有明显的保护作用,这些研究进一步提示内源性谷氨酸(Glutamate,Glu)的大量释放过度激活NMDA受体参与急性肺损伤的发生发展过程。但为证明内源性Glu的大量释放过度激活NMDA受体在急性肺损伤的发生中具有普遍意义,尚有待在不同模型上进一步证实。
方法(1)建立小鼠急性油酸肺损伤模型;(2)测量肺湿重和干重的比值(W/D)并观察肺组织病理变化,以反映肺组织的损伤程度;(3)测定支气管肺泡灌洗液中蛋白和白细胞含量,以反映支气管肺泡毛细血管通透性变化;(4)生化测定肺组织髓过氧化物酶(MPO),反映氧化损伤时的肺炎性改变;(5)RT-PCR和免疫组化分别检测CTP:磷酸胆碱二胞苷酰基转移酶α(CTP:phosphocholinecytidylyltransferase alpha,CCTα)mRNA和蛋白水平,反映CCTα转录合成的变化。
结果油酸(0.1 ml/kg)尾静脉注射4 h可引起肺组织肺指数、肺湿干重比W/D增加、肺组织MPO活性增加,支气管肺泡灌洗液中蛋白和白细胞含量明显增加,并引起肺组织CCTαmRNA和蛋白水平的明显减低,病理切片示水肿、炎症渗出明显。NMDA受体的阻断剂MK-801(0.1mg/kg,ip)预处理30 min可减轻油酸引起的上述变化。
结论油酸引起明显以炎性渗出为主的急性肺损伤,肺内NMDA受体的激活参与油酸急性肺损伤的发生,并引起CCTα表达的下调。
第二章NMDA抑制CCTα表达的转录调控机制
研究背景CTP:磷酸胆碱二胞苷酰基转移酶(CTP:phosphocholinecytidylyltransferase alpha,CCTα)是磷脂酰胆碱(phosphatidylcholine,PC)合成中的关键调控酶。CCTα基因近端启动子区包含多个与细胞生长、分化密切相关的转录因子Sp1(specificity protein 1)结合位点。探讨Sp1在CCTα启动转录中的作用具有一定的意义。在急性肺损伤(acute lung iniury,ALI)及ARDS等肺部损伤疾病中,肺表面活性物质(pulmonary surfactant,PS)系统功能的异常并参与肺损伤的发生过程。本室前期研究证明一定剂量NMDA作用后,肺Ⅱ型上皮细胞合成CCT mRNA水平、CCTα蛋白表达水平均下降。本研究旨在观察NMDA受体激活后Sp1的改变,探讨NMDA抑制CCTα表达的分子机制。
方法(1)萤光素酶报告基因活性检测CCTα启动子活性;(2)荧光定量PCR定量检测Sp1表达质粒后CCTαmRNA;(3)Western blot检测A549细胞转染Sp1表达质粒后CCTα蛋白含量表达水平;(4)Western blot检测A549细胞经NMDA处理后Sp1蛋白含量表达水平;(5)荧光定量PCR定量检测A549细胞经NMDA处理后Sp1mRNA水平;(6)EMSA检测CCTα启动子上Sp1的DNA结合活性及NMDA处理对其影响。
结果转染Sp1真核表达质粒30 h后,A549细胞CCTα核心启动子报告基因相对萤光素酶活性增加,A549细胞CCTαm RNA表达水平表达水平增高。转染Sp1真核表达质粒36 h后,CCTα蛋白表达水平表达水平增高。A549细胞经NMDA处理8 h后,Sp1蛋白表达明显下降,并呈时间、剂量依赖。Sp1 mRNA水平没有明显的改变。EMSA检测显示,NMDA处理后A549细胞的核蛋白中转录因子Sp1与DNA的结合活性下调。
结论转录因子Sp1促进A549细胞CCTα的启动子活性,增加CCTα的合成表达。NMDA通过下调核内Sp1蛋白与DNA结合活性而抑制CCTα的表达。
Chapter 1 Effect of MK-801 on oleic acid-induced acute lung injury in mice
Background Acute respiratory distress syndrome(ARDS)is a common clinical syndrome.The exact pathogenesis of ARDS,however, is not well characterized.Pulmonary neutrophil sequestration and the activation of neutrophils and alveolar macrophages play key roles in the pathogenesis of ARDS.It has been shown that glutamate released from activated neutrophils acts as a source of excitotoxic injury of other cells. Both macrophages and activated neutrophils release glutamate.Said et al.reported that administration of high concentrations of glutamate or glutamate agonist NMDA can elicit an acute,high-permeability pulmonary edema.In recent years,we find that the NMDA receptor antagonist MK-801(dizocilpine)attenuates lipopolysaccharide(LPS) and hyperoxia-induced lung injury.These findings suggested that lung injury(caused by LPS and hyperoxia)could be mediated partly by endogenous glutamate release and toxic overactivation of NMDA receptors.Therefore,glutamate receptors may serve novel,yet to-be characterized injury factor during acute lung injury.Further studies in different animal models of lung injury are required before assuming their universal significance.
Methods(1)Oleic acid(0.1ml/kg)was injected via the caudal vein to induce acute lung injury model in mice.(2)Lung wet-to-dry weight ratio (W/D)and histopathological examination were used to evaluate the severity of pulmonary edema.(3)Lung tissue myeloperoxidase(MPO) activity was quantified by using commercial kits as a reflection of neutrophil sequestration.(4)Total neutrophil count and total protein concentration in bronchoalveolar lavage fluid(BALF)were determined to reflect changes in alveolar-capillary permeability.(5)The mRNA level of CCTαin the lung was measured by RT-PCR,and the expression of CCTαprotein was semi-quantified by immunohistochemistry.
Results(1)Oleic acid-induced increases in the concentration of total protein and the numbers of neutrophils in BALF were significantly attenuated in MK-801(0.1mg/kg,ip)pretreated mice;(2)MK-801 pretreatment also resulted in a significant protection in lung tissue tested against oleic acid-induced acute lung injury via decreasing W/D ratio, MPO activity.(3)The CCTαexpression decreased in oleic acid-induced lung injury model,both at protein and mRNA levels. MK-801 pretreatment attenuated oleic acid-induced down-regulation of CCTαexpression in the lung.
Conclusion Oleic acid caused an acute lung damage characterized by severe edema formation and pulmonary inflammation in mice. Endogenous NMDA receptor activation may play an important role in mediating oleic acid-induced lung injury.In this model,expression of CCTαwas decreased.
Chapter 2 Study on the transcriptional regulation mechanism of CTP:phosphocholine cytidylyltransferase alpha expression inhibition by NMDA
Background CTP:phosphocholinecytidylyltransferase alpha(CCTα) is the major rate-limiting enzyme for phosphatidylcholine(PC)synthesis. The promoter of CCTαis GC rich,and contains several binding sites for the specificity protein 1(Sp1)transcription factor,which is thought to play an important role in regulating cell growth and differentiation.The dysfunction of pulmonary surfactant(PS)is thought to be a important factor during the development of acute lung injury(including ARDS). Previous work in our group has demonstrated NMDA can repress CCTαmRNA and protein expression in pulmonary alveolar typeⅡcells.In this study,we examined the changes in Sp1 expression after NMDA treatment and the molecular mechanism of transcriptional regulation of inhibition of CCTαexpression by NMDA.
Methods(1)CCTαpromotor activity was measured using Dual-luciferase reporter assay system.(2)CCTαmRNA expression was measured by RT-PCR after 30 h of transfection with Sp1(pEVR2-Sp1) expression plasmid.(3)CCTαprotein level was measured by Western blot after 36 h of transfection with pEVR2-Sp1 plasmid.(4)Sp1 protein in nuclear extracts after NMDA treatment was measured by Western blot.Sp1 mRNA was measured by RT-PCR,and Sp1 DNA binding activity was measured by EMSA.
Results Transfection of the A549 cells with the Sp1 expression plasmid,pEVR2-Sp1,resulted in an increase in promoter activity,and as well as increases in CCTαmRNA and protein.Treatment of A549 cells with NMDA for 8h,the level of Sp1 protein decreased in a dose- and time-dependent manner in nuclear protein.But the level of Sp1 mRNA did not change significantly.EMSA showed that NMDA inhibited the DNA binding activity of Splin A549 cells.
Conclusion Sp1 promotes the CCTαpromoter acticity and increase expression of CCTαin A549 cells.NMDA receptor activation inhibites CCTαexpression by decreaseing Sp1 protein and DNA binding activity in neuclear of A549 cells.
引文
[1]Valera E,Fernandez-Salguero PM,et al.Neuroprotection against excitotoxicity by N-alkylglycines in rat hippocampal neurons.Neuromolecular Med,2002,2(3):271-80.
[2]Sargolini F,Florian C,Oliverio A,et al.Differential involvement of NMDA and AMPA receptors within the nucleus accumbens in consolidation of information necessary for place navigation and guidance strategy of mice.Learn Mem.2003,10(4):285-92.
[3]Yoo KY,Hwang IK,Lim BO,et al.Berberry extract reduces neuronal damage and N-Methyl-D-aspartate receptor 1 immunoreactivity in the gerbil hippocampus after transient forebrain ischemia.Biol Pharm Bull,2006,29(4):623-8.
[4]Gill SS,Pulido OM.Glutamate Receptors in Peripheral Tissues:Current Knowledge,Future Research,and Implications for Toxicology.Toxicologic Pathology,2001,29(2):208-223.
[5]Kondo H,Feng GG;Nishiwaki K,et al.A role for 1-glutamate ionotropic receptors in the development of rat neurogenic pulmonary edema.Eur J Pharm,2004,499:257-263.
[6]Collard CD,Park KA,Montalto MC.Neutrophil-derived glutamate regulates vascular endothelial barrier function.J Biol Chem,2002,277(17):14801-11.
[7]Jiang ZG,Piggee C,Heyes MP,et al.Glutamate is a mediator of neurotoxicity in secretions of activated HIV-1-infected macrophages.J Neuroimmuncl,2001,117(1-2):97-107.
[8]Ardawi MS.Glutamine and alanine metabolism in lungs of septic rats.Clin Sci(Lond),1991,81(5):603-9.
[9]Said SI,Berisha HI,Pakbaz H.Excitotoxicity in the lung:N-methyl-D-aspartate-induced,nitric oxide-dependent,pulmonary edema is attenuated by vasoactive intestinal peptide and by inhibitors of poly(ADP-ribose)polymerase.Proc Natl Acad Sci USA,1996,93(10):4688-92.
[10]申丽,罗自强。谷氨酸的肺损伤作用及人参皂甙Rg1的保护作用:[博士学位论文],长沙:中南大学,2003,
[11]王鹏程,罗自强。NMDA受体在内毒素致肺损伤中的作用:[硕士学位论文],长沙:中南大学,2003.
[12]Tang FG,Yue SJ,Luo ZQ,et al.Role of N-Methyl-D-Aspartate Receptor Hyperoxia-Induced Lung injury.Pediatric Pulmonology,2005,40:437-44.
[13]Dickman KG,Youssef JG,Mathew SM,et al.Ionotropic glutamate receptors in lungs and airways:molecular basis for glutamate toxicity.Am J Respir Cell Mol Biol,2004,30(2):139-44.
[14]申丽,罗自强。NMDA受体激活引起肺损伤及机制研究:[博士学位论文],长沙:中南大学,2006.
[15]Nagaoka M,Shiraishi Y,Sugiura Y.Selected base sequence outside the target binding site of zinc finger protein Spl.Nucleic Acids Res,2001,29(24):4920-9.
[16]Wang L,Magdaleno S,Tabas I,et al.Early embryonic lethality in mice with targeted deletion of the CTP:phosphocholine cytidylyltransferase alpha gene(Pcytla).Mol Cell Biol,2005,25(8):3357-63.
[17]Duffett M,Choong K,Ng V,et al.Surfactant therapy for acute respiratory failure in children:a systematic review and meta-analysis.Crit Care,2007,11(3):R66.
[18]Davidson WJ,Dorscheid D,Spragg R,et al.Exogenous pulmonary surfactant for the treatment of adult patients with acute respiratory distress syndrome:results of a meta-analysis.Crit Care,2006,10(2):R41.
[19]Wu JX,Xu MY,Zhang FJ,et al.The effect of hydroxyethyl starch on capillary permeability in a rat model of acute lung injury.Zhonghua Ma Zui Xue Za Zhi,2003,23:197-200.
[20]王祥瑞。急性肺损伤:基础与临床,北京:中国协和医科大学出版社,2005,300-310.
[21]Shah NS,Nakayama DK,Jacob TD,et al.Efficacy of inhaled nitric oxide in oleic acid-induced acute lung injury.Crit Care Med,1997,25:153-153.
[22]Xu RF,Li TT,Feng XY,et al.Therapeutic Effect of Hyperoxygenated Solution on Acute Lung Injury Induced by Oleic Acid.Eur Surg Res,2008,41(1):37-43
[23]梅双,赵金垣,温韬。油酸性急性肺损伤启动机制的实验研究。中国工业医学杂志,2007,20(2)67-71.
[24]Perl M,Lomas-Neira J,Chung CS,et al.Acute Lung Injury:Neutrophils,Epithelial Cell Death & Inflammation:A Unifying Hypothesis.Mol Med,2008, 27.Articles Published Online First.
[25]绪广林,姚琳,余书勤。表没食子儿茶素没食子酸酯对小鼠油酸型肺损伤的保护作用。药学学报,2005,40(3):231-235.
[26]周治明,段开明,罗颖。乌司他丁对家兔油酸型肺损伤后血管外肺水肿和肺换气功能的影响,中华现代外科学杂志,2006,3(7):584-85.
[27]Wittwer T,Franke UF,Ochs M,et al.Inhalative pre-treatment of donor lungs using the aerosolized prostacyclin analog iloprost ameliorates reperfusion injury.J Heart Lung Transplant,2005,24(10):1673-9.
[28]Perl M,Lomas-Neira J,Chung CS.Acute Lung Injury:Neutrophils,Epithelial Cell Death & Inflammation:A Unifying Hypothesis.Mol Med,2008,Articles Published Online First.
[29]Lomas-Neira JL,Chung CS,Wesche DE,et al.In vivo gene silencing(with siRNA)of pulmonary expression of MIP-2 versus KC results in divergent effects on hemorrhage-induced,neutrophil-mediated septic acute lung injury J Leukoc Biol,2005,77(6):846-53.
[30]Lau D,Mollnau H,Eiserich JP,et al.Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins.Proc Natl Acad Sci USA,2005,102:431-36.
[31]Seymour J.Klebanoff.Myeloperoxidase:friend and foe.Journal of Leukocyte Biology,2005,77:598-625.
[32]Nys M,Preiser JC,Deby-Dupont G,et al.Nitric oxide-related products and myeloperoxidase in bronchoalveolar lavage fluids from patients with ALI activate NF-kappa B in alveolar cells and monocytes.Vascul Pharmacol,2005,43(6):425-33.
[33]Suratt BT,Parsons PE.Mechanisms of acute lung injury/acute respiratory distress syndrome.Clin Chest Med,2006,27(4):579-89.
[34]Calfee CS,Matthay MA:Nonventilatory treatments for acute lung injury and ARDS.Chest,2007,131:913-20.
[35]Spragg RG;Lewis JF,Walmrath HD,et al.Effect of recombinant surfactant protein C-based surfactant on the acute respiratory distress syndrome.N Engl J Med,2004,351:884-92.
[36]Rossaint R,Falke KJ,Lopez F,et al.Inhaled nitric oxide for the adult respiratory distress syndrome.N Engl J Med,1998,328:399-405.
[37]Slotman GJ,Burchard KW,D'Arezzo A,et al.Ketoconazole prevents acute respiratory failure in critically ill surgical patients.J Trauma,1988,28:648-54.
[38]Sprung CL,Caralis PV,Marcial EH,et al.The effects of highdose corticosteroids in patients with septic shock.A prospective,controlled study.N En Med,1984,311:1137-1143.
[39]Wiedemann HP,Arroliga AC,Komara J,et al.The Acute Respiratory Distress Syndrome Network:Randomized,placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome.Crit Care Med,2002,30(1):1-6.
[40]Ito K,Mizutani A,Kira S,et al.Effect of Ulinastatin,a human urinary trypsin inhibitor,on the oleic acidinduced acute lung injury in rats via the inhibition of activated leukocytes.Injury,2005,36(3),387-394.
[41]Ridsdale R,Tseu I,Roth-Kleiner M,et al.Increased phosphatidylcholine production but disrupted glycogen metabolism in fetal type Ⅱ cells of mice that overexpress CTP:phosphocholine cytidylyltransferase.J Biol Chem,2004,279(53):55946-57.
[42]Zhou J,Ryan AJ,Medh J,et al.Oxidized lipoproteins inhibit surfactant phospha tidylcholine synthesis via calpain-mediated cleavage of CTP:Phosphorcholine cytidylyltransferase.J Biol Chem,2003,278(39):37032-40.
[43]Mallapalli RK,Ryan AJ,Salome RG,et al.Tumor necrosis factor-alpha inhibits expression of CTP:phosphocholine cytidylyltransferase.J Biol Chem,2000,275(13):9699-708
[44]Sun Y,Wang YQ,Zhong JG,et al.Influence of porcine pulmonary surfactant administered at different time on therapeutic effects in rats with oleic acid induced acute lung injury.Zhongguo Wei Zhong Bing Ji Jiu Yi Xue,2008,20(2):88-91.
[45]崔社怀,郭先健。急性低氧油酸肺损伤表面活性物质相关蛋白表达的变化。中华结核和呼吸感染,1998,2(24):89-93.
[46]Rosemary B.Comell,,Ingrid C.Northwood.Regulation of CTP:phosphocholine cytidylyltransferase by amphitropism and relocalization.TIBS,2000,25:441-447.
[47]Ross Ridsdale,Irene Tseu,Jinxia Wang,etal.CTP:Phosphocholine Cytidylyltransferaseα Is a Cytosolic Protein in Pulmonary Epithelial Cells and Tissues.J Biol Chem.2001,276(52):49148-49155.
[48]Sugimoto H,Banchio C,Vance DE.Transcriptional regulation of phosphatidylcholine biosynthesis. Prog Lipid Res, 2008, 6:204-20.
[49] Karim M, Jackson P, Jackowski SMol. Gene structure, expression and identification of a new CTP: phosphocholine cytidylyltransferase beta isofonn, Biochim Biophys Acta, 2003, 1633(1): 1-12.
[50] Sugimoto H, Okamura K, Sugimoto S, et al. Sp1 is a co-activator with Ets-1, and Net is an important repressor of the transcription of CTP:phosphocholine cytidylyltransferase alpha. J Biol Chem, 2005,280(49):40857-66.
[51] Banchio C, Lingrell S, Vance DE. Sp-1 binds promoter elements that are regulated by retinoblastoma and regulate CTP:phosphocholine cytidylyltransferase-alpha transcription.J Biol Chem, 2007,282(20):14827-35.
[52] Bakovic M, Waite KA, Vance DE. Functional significance of Spl, Sp2, and Sp3 transcription factors in regulation of the murine CTP:phosphocholine cytidylyltransferase alpha promoter. J Lipid Res, 2000, 41(4):583-94.
[53] Bouwman P, Philipsen S. Regulation of the activity of Sp1-related transcription factors. Mol Cell Endocrinol., 2002, 195(1-2): 27-38.
[54] Zhou JM, You Y, Zabner J, et al. The CCT Promoter Directs High-Level Transgene Expression in Distal Lung Epithelial Cell Lines. Am J Respir Cell Mol Biol, 2004, 30: 61-68
[55] Jie Wan, Brian A. Carr, N. Shane Cutler, et al. Spl and Sp3 regulate basal transcription of the human CYP2F1 gene.Drug Metabolish and Disposition, 2005, 30(8):1244-1253.
[56] Zhao C, Meng A. Sp1-like transcription factors are regulators of embryonic development in vertebrates. Dev Growth Differ, 2005, 47(4): 201-11.
[57] GSuske. The Sp-family of transcription factors. Gene, 1999, 238:291-300.
[58] Li L, He SH, Sun JM, et al. Gene regulation by Spl and Sp3. Biochemistry and Cell Biology, 2005, 82: 460-71.
[59] Rickers A, Peters N, Badock V, et al. Cleavage of transcription factor SP1 by caspases during anti-IgM-induced B-cell apoptosis. J Biochem, 1999, 261:269-74.
[60] Chu S, Ferro TJ. Sp1: regulation of gene expression by phosphorylation. Gene, 2005, 348(1): 1-11.
[61] Sugimoto H, Banchio C, Vance DE. Transcriptional regulation of phosphatidylcholine biosynthesis.Progress in Lipid Research, 2008, 47 : 204-20.
[62] Banchio C, Schang LM, Vance DE. Phosphorylation of Spl by cyclin-dependent kinase 2 modulates the role of Spl in CTP:phosphocholine cytidylyltransferase alpha regulation during the S phase of the cell cycle. J Biol Chem., 2004,279(38):40220-6.
[63] Banchio C, Schang LM, Vance DE. Activation of CTP: phosphocholine cytidylyltransferase alpha expression during the S phase of the cell cycle is mediated by the transcription factor Spl. J Biol Chem.2003, 278(34): 32457-64.
[1]Clement JM,Kent C.CTP:phosphocholine cytidylyltransferase:insights into regulatory mechanisms and novel functions.Biochem Biophys Res Commun,1999,257(3):643-50.
[2]Waite K,Tang W,Tabas I,et al.Transcriptional activation of the murine CTP:phosphocholine cytidylyltransferase gene(Ctpct):combined action of upstream stimulatory and inhibitory cis-acting elements.Biochim Biophys Acta,1999,1438(1):147-65.
[3]Lykidis A,Murti KG,Jackowski S.Cloning and characterization of a second human CTP:phosphocholine cytidylyltransferase.J Biol Chem,1998,273(22):14022-9.
[4]Karim M,Jackson P,Jackowski S.Gene structure,expression and identification of a new CTP:phosphocholine cytidylyltransferase beta isoform.Biochim Biophys Acta,2003,1633(1):1-12.
[5]Ridsdale R,Tseu I,Wang J,et al.CTP:phosphocholine cytidylyltransferase alpha is a cytosolic protein in pulmonary epithelial cells and tissues.J Biol Chem,2001,276(52):49148-55.
[6]DeLong C J,Qin L,Cui Z.Nuclear localization of enzymatically active green fluorescent protein-CTP:phosphocholine cytidylyltransferase alpha fusion protein is independent of cell cycle conditions and cell types.J Biol Chem,2000,275(41):32325-30
[7]Rosemary B.Cornell,Ingrid C.Northwood.Regulation of CTP:phosphor-choline cytidylyltransferase by amphitropism and relocalization.Trends in Biochemical Sciences,2000,25(9):441-447.
[8]Joel M.Clement and Claudia Kent.CTP:Phosphocholine Cytidylyltransferase:Insights into Regulatory Mechanisms and Novel Functions.Biochemical and Biophysical Research Communications,1999,257:643-650.
[9]Wang L,Magdaleno S,Tabas I,et al.Early embryonic lethality in mice with targeted deletion of the CTP:phosphocholine cytidylyltransferase alpha gene (Pcytla).Mol Cell Biol,2005,25(8):3357-63.
[10]罗自强,冯丹丹,周伏文。低浓度内皮素-1对活性氧抑制肺表面活性物质脂质合成的保护,生理学报,2002,2(54):89-93.
[11]Tian Y,Zhou R,Rehg JE.Role of phosphocholine cytidylyltransferase alpha in lung development.Mol Cell Biol.2007,7(3):975-82.
[12]Zhou JM,You Y,J Zabner,et al.The CCT Promoter Directs High-Level Transgene Expression in Distal Lung Epithelial Cell Lines.Am J Respir Cell Mol Biol,2004,30(1):61.
[13]Zuo YY,Veldhuizen RA,Neumann AW,et al.Current perspectives in pulmonary surfactant - Inhibition,enhancement and evaluation.Biochimica et Biophysica Acta,2008,Epub ahead of print.
[14]A.Gunther,R.Schmidt,J.Harodt,T,et al.Bronchoscopic administration of bovine natural surfactant in ARDS and septic shock:impact on biophysical and biochemical surfactant properties.Eur Respir J,2002,19:797-804.
[15]Odalys Blanco,Jesus Pérez-Gil.Biochemical and pharmacological differences between preparations ofexogenous natural surfactant used to treat Respiratory Distress Syndrome:Role of the different components in an efficient pulmonnary surfactant.Eur J Pharm,2007,(568):1-15.
[16]Tian Y,Zhou R,Rehg JE,et al.Role of phosphocholine cytidylyltransferase alpha in lung development.Mol Cell Biol.2007,27(3):975-82.
[17]McCoy DM,Fisher K,Robichaud J,et al.Transcriptional regulation of lung cytidylyltransferase in developing transgenic mice.Am J Respir Cell Mol Biol.2006,35(3):394-402.
[18]Vivekananda J,Smith D,King RJ.Sphingomyelin metabolites inhibit sphingomyelin synthase and CTP:phosphocholine cytidylyltransferase.Am J Physiol Lung Cell Mol Physiol,2001,281(1):98-107.
[19]Choline Deficiency Causes Translocation of CTP:Phosphocline Cytidyltansferase from Cytosol to Endoplasmic Reticulumn in Rat Liver.J Biol Chem.200,265(8):1 62-8.
[20]Suzanne Jackowski,Paolo Fagone.CTP:Phosphocholine Cytidylyltransferase:Paving the Way from Gene to Membrane.J Biol Chem.2005,280(2):853-6.
[21]龚小慧,胡肖伟,孙波。吸人一氧化氮对内毒素性肺损伤大鼠肺磷脂合成的影响。中华急诊医学杂志,2004,13(6):382-5.
[22]Li J,Marsh JJ,Spragg RG.Effect of CTP:phosphocholine cytidylyltransferase overexpression on the mouse lung surfactant system.Am J Respir Cell Mol Biol,2002,(6):709-15.
[23]Storey MK,Byers DM.Decreased phosphatidylcholine biosynthesis and abnormal distribution of CTP:phosphocholine cytidylyltransferase in cholesterol auxotrophic Chinese hamster ovary cells. J Lipid Res, 1997, (4):711-22.
[24] Jacobs RL, Lingrell S, Zhao Y, et al. Hepatic CTP:phosphocholine cytidylyltransferase-alpha is a critical predictor of plasma high density lipoprotein and very low density lipoprotein. J Biol Chem, 2008, 283(4): 2147-55.
[25] Mallampalli RK, Ryan AJ, Carroll, JL, et al. Lipid deprivation increases surfactant phosphatidylcholine synthesis via a sterol-sensitive regulatory element within the CTP:phosphocholine cytidylyltransferase promoter. Biochem J, 2002,362:81-88.
[26] Zhou J., Ryan AJ, Medh J, et al. Oxidized lipoproteins inhibit surfactant phosphatidylcholine synthesis via calpain-mediated cleavage of CPT:Phosphocholine cytidylyltransferasen. J Biol Chem, 2003, 278: 37032-40.
[27] Lagace TA, Miller JR, Ridgway ND. Caspase processing and nuclear export of CTP:phosphocholine cytidylyltransferase alpha during farnesol-induced apoptosis. Mol Cell Biol, 2002, 2(13):4851-62.
[28] Agassandian M, Zhou J, Tephly LA, et al. Oxysterols inhibit phosphatidylcholine synthesis via ERK docking and phosphorylation of CTP:phosphocholine cytidylyltransferase. J Biol Chem, 2005, 280(22):21577-87.
[29] Chen BB, Mallampalli RK.Calmodulin binds and stabilizes the regulatory enzyme, CTP: phosphocholine cytidylyltransferase. J Biol Chem. 2007,282 (46):33494-506
[30] Mallampalli. RK,Ryan AJ,Salome RG,et al. Tumor necrosis factor-alpha inhibits expression of CTP:phosphocholine cytidylyltransferase. J Biol Chem.2000, 275(13):9699-708.
[31] Kitos TE, Choi CM, Cornell RB. Angiotensin stimulates phosphatidylcholine synthesis via a pathway involving diacylglycerol, protein kinase C, ERK1/2, and CTP:phosphocholine cytidylyltransferase. Biochim Biophys Acta. 2006, 1761 (2):272-9.
[32] Wang Y, Kent C. Effects of altered phosphorylation sites on the properties of CTP: phosphocholine cytidylyltransferase. J Biol Chem, 1995, 270:17843-9.
[33] Jamil H, Utal AK, Vance DE. Evidence that cyclic AMP induced nhibition of phosphatidylcholine biosynthesis is caused by a decrease in cellular diacylglycerol levels in cultured rat hepatocytes.J Biol Chem,1992,267:1752-60.
[34]Shiratori Y,Houweling M,Zha X,Tabas I.Stimulation of CTP:phosphocholine cytidylyltransferase by free cholesterol loading of macrophages involves signaling through protein dephosphorylation.J Biol Chem.1995,270:29894-903.
[35]Mallampalli RK.Oxysterols inhibit phosphatidylcholine synthesisvia ERK docking and phosphorylation of CTP:phosphocholine cytidylyltransferase.J Biol Chem,2005,280:21577-87.
[36]Li L,Luo ZQ,Zhou FW,et al.Effect of vasoactive intestinal peptide on pulmonary surfactants phospholipid synthesis in lung explants.Acta Pharmacol Sin,2004,25(12):1652-8.
[37]McCoy DM,Fisher K,Robichaud J,Ryan AJ,Mallampalli RK.Transcriptional regulation of lung cytidylyltransferase in developing transgenic mice.Am J Respir Cell Mol Biol,2006,35(3):394-402.
[38]Sugimoto H.Transcriptional regulation of CTP:phosphocholine cytidylyltransferase in phospholipid biosynthesis.Seikagaku.2007,79(10):968-72.
[39]Sugimoto H,Banchio C,Vance DE.Transcriptional regulation of phosphatidylcholine biosynthesis.Prog Lipid Res,2008,47:204-220.
[40]Sugimoto H,Okamura K,Sugimoto S,et al.Sp1 is a co-activator with Ets-1,and Net is an important repressor of the transcription of CTP:phosphocholine cytidylyltransferase alpha.J Biol Chem.2005,280(49):40857-66.
[41]Bakovic M,Waite KA,Vance DE.Functional significance of Sp1,Sp2,and Sp3 transcription factors in regulation of the murine CTP:phosphocholine cytidylyltransferase alpha promoter.J Lipid Res.2000,41(4):583-94.
[42]薛丽香,翁默,吴军峰。Sp1和Sp3介导的转录调控。 中国生物化学与分子生物学报,2006,22(2):106-110.
[43]Claudia B,Luis M.S,Dennis EV.Activation of CTP:Phosphocholine Cytidylyltransferase Expression during the S Phase of the Cell Cycle Is Mediated by the Transcription Factor Sp1.J Biol Chem,2003,278(34):32457-64.
[44]Hiroyuki S,Marica B,Satoshi Y.Identification of Transcriptional Enhancer Factor-4 as a Transcriptional Modulator of CTP:Phosphocholin Cytidylyltransferase a. J Biol Chem, 2001, 276(15): 12338-44.
[45] Ridgway ND, Lagace TA. Regulation of the CDP-choline pathway by sterol regulatory element binding proteins involves transcriptional and post-transcriptional mechanisms. Biochem J, 2003, 372(3):811-9.
[46] Udvadia AJ, Templeton DJ, Horowitz JM. Functional interactions between the retinoblastoma (Rb) protein and Sp-family members: superactivation by Rb requires amino acids necessary for growth suppression. J Biol Chem. 2007, 282(20): 14827-35.
[47] Banchio C, Lingrell S, Vance DE. Sp-1 binds promoter elements that are regulated by retinoblastoma and regulate CTP:phosphocholine cytidylyltransferase-alpha transcription. J Biol Chem, 2007,282(20):14827-35.
[48] Tseu I, Ridsdale R, Liu J, et al. Cell cycle regulation of pulmonary phosphatidylcholine synthesis. Am J Respir Cell Mol Biol. 2002, 26(4):506-15.
[49] Jackowski S. Coordination of membrane Phospholipid synthesis with the cell cycle. J Biol Chem.1994, 269(5):3858-67.
[50] Golfman LS,Bakovic M, Vance DE.Transcription of the CTP:phosphocholine cytidylyltransferase alpha gene is enhanced during the S phase of the cell cycle. J Biol Chem. 2001, 76 (47):43688-92.
[51] Suzanne Jackowski .Cell Cycle Regulation of Membrane Phospholipid Metabolism. J Biol Chem. 1996, 271(34): 20219-22.
[52] Banchio C, Schang LM, Vance DE. Phosphorylation of Sp1 by cyclin-dependent kinase 2 modulates the role of Spl in CTP: phosphocholine cytidylyltransferase alpha regulation during the S phase of the cell cycle. J Biol Chem. 2004, 279 (38):40220-6.
[53] Tseu I, Ridsdale R, Liu J, Wang J, et al. Cell cycle regulation of pulmonary phosphatidylcholine synthesis.J Respir Cell Mol Biol, 2002, 26:506-15.
[54] Sewack G F, Elis T W, Hansen U. Binding of TATA binding Protein to a naturally positioned nucleosome is facilitated by histone acetylation. Mol Ceil Biol, 2001, 21: 1404-15
[55] KouzaridesT. Histone acetylases and deacetylases in ceil proliferation. Curr Opin Genet Dev, 1999, 9: 40-8.
[56] Cheng M, Olivier P, Diehl J A, et al. The p21(Cipl) and p27(Kip1) CDK 'inhibitors' are essential activators of cyclin D-dependent kinases in murine fibroblasts. EMBO J, 1999, 18(6): 1571-1583.
[57] Vigushini D M, Coombes R C. Histone Deacetylase inhibitors in cancer treatment. Anticancer Drugs, 2002, 13(1): 1-13
[58] Banchio C, Lingrell S, Vance DE. Role of histone deacetylase in the expression of CTP:phosphocholine cytidylyltransferase alpha. J Biol Chem, 2006,281:10010-5.
[59] Doetzlhofer A, Rotheneder H, Lagger G, et al. Histone deacetylase 1 can repress transcription by binding to Sp1. Mol Cell Biol, 1999,19:5504-11.
[60] Liu H, Dibling B, Spike B,et al. New roles for the RB tumor suppressor protein.Curr Opin Genet.Dev, 2004,4:55-64.
[61] Banchio C, Lingrell S, Vance DE. Sp-1 binds promoter elements that are regulated by Rb and regulate CTP: phosphocholine cytidylyltransferase-alpha transcription. Biol Chem, 2007, 282:14827-45.
[2]Sargolini F,Florian C,Oliverio A,et al.Differential involvement of NMDA and AMPA receptors within the nucleus accumbens in consolidation of information necessary for place navigation and guidance strategy of mice.Learn Mem.2003,10(4):285-92.
[3]Yoo KY,Hwang IK,Lim BO,et al.Berberry extract reduces neuronal damage and N-Methyl-D-aspartate receptor 1 immunoreactivity in the gerbil hippocampus after transient forebrain ischemia.Biol Pharm Bull,2006,29(4):623-8.
[4]Gill SS,Pulido OM.Glutamate Receptors in Peripheral Tissues:Current Knowledge,Future Research,and Implications for Toxicology.Toxicologic Pathology,2001,29(2):208-223.
[5]Kondo H,Feng GG;Nishiwaki K,et al.A role for 1-glutamate ionotropic receptors in the development of rat neurogenic pulmonary edema.Eur J Pharm,2004,499:257-263.
[6]Collard CD,Park KA,Montalto MC.Neutrophil-derived glutamate regulates vascular endothelial barrier function.J Biol Chem,2002,277(17):14801-11.
[7]Jiang ZG,Piggee C,Heyes MP,et al.Glutamate is a mediator of neurotoxicity in secretions of activated HIV-1-infected macrophages.J Neuroimmuncl,2001,117(1-2):97-107.
[8]Ardawi MS.Glutamine and alanine metabolism in lungs of septic rats.Clin Sci(Lond),1991,81(5):603-9.
[9]Said SI,Berisha HI,Pakbaz H.Excitotoxicity in the lung:N-methyl-D-aspartate-induced,nitric oxide-dependent,pulmonary edema is attenuated by vasoactive intestinal peptide and by inhibitors of poly(ADP-ribose)polymerase.Proc Natl Acad Sci USA,1996,93(10):4688-92.
[10]申丽,罗自强。谷氨酸的肺损伤作用及人参皂甙Rg1的保护作用:[博士学位论文],长沙:中南大学,2003,
[11]王鹏程,罗自强。NMDA受体在内毒素致肺损伤中的作用:[硕士学位论文],长沙:中南大学,2003.
[12]Tang FG,Yue SJ,Luo ZQ,et al.Role of N-Methyl-D-Aspartate Receptor Hyperoxia-Induced Lung injury.Pediatric Pulmonology,2005,40:437-44.
[13]Dickman KG,Youssef JG,Mathew SM,et al.Ionotropic glutamate receptors in lungs and airways:molecular basis for glutamate toxicity.Am J Respir Cell Mol Biol,2004,30(2):139-44.
[14]申丽,罗自强。NMDA受体激活引起肺损伤及机制研究:[博士学位论文],长沙:中南大学,2006.
[15]Nagaoka M,Shiraishi Y,Sugiura Y.Selected base sequence outside the target binding site of zinc finger protein Spl.Nucleic Acids Res,2001,29(24):4920-9.
[16]Wang L,Magdaleno S,Tabas I,et al.Early embryonic lethality in mice with targeted deletion of the CTP:phosphocholine cytidylyltransferase alpha gene(Pcytla).Mol Cell Biol,2005,25(8):3357-63.
[17]Duffett M,Choong K,Ng V,et al.Surfactant therapy for acute respiratory failure in children:a systematic review and meta-analysis.Crit Care,2007,11(3):R66.
[18]Davidson WJ,Dorscheid D,Spragg R,et al.Exogenous pulmonary surfactant for the treatment of adult patients with acute respiratory distress syndrome:results of a meta-analysis.Crit Care,2006,10(2):R41.
[19]Wu JX,Xu MY,Zhang FJ,et al.The effect of hydroxyethyl starch on capillary permeability in a rat model of acute lung injury.Zhonghua Ma Zui Xue Za Zhi,2003,23:197-200.
[20]王祥瑞。急性肺损伤:基础与临床,北京:中国协和医科大学出版社,2005,300-310.
[21]Shah NS,Nakayama DK,Jacob TD,et al.Efficacy of inhaled nitric oxide in oleic acid-induced acute lung injury.Crit Care Med,1997,25:153-153.
[22]Xu RF,Li TT,Feng XY,et al.Therapeutic Effect of Hyperoxygenated Solution on Acute Lung Injury Induced by Oleic Acid.Eur Surg Res,2008,41(1):37-43
[23]梅双,赵金垣,温韬。油酸性急性肺损伤启动机制的实验研究。中国工业医学杂志,2007,20(2)67-71.
[24]Perl M,Lomas-Neira J,Chung CS,et al.Acute Lung Injury:Neutrophils,Epithelial Cell Death & Inflammation:A Unifying Hypothesis.Mol Med,2008, 27.Articles Published Online First.
[25]绪广林,姚琳,余书勤。表没食子儿茶素没食子酸酯对小鼠油酸型肺损伤的保护作用。药学学报,2005,40(3):231-235.
[26]周治明,段开明,罗颖。乌司他丁对家兔油酸型肺损伤后血管外肺水肿和肺换气功能的影响,中华现代外科学杂志,2006,3(7):584-85.
[27]Wittwer T,Franke UF,Ochs M,et al.Inhalative pre-treatment of donor lungs using the aerosolized prostacyclin analog iloprost ameliorates reperfusion injury.J Heart Lung Transplant,2005,24(10):1673-9.
[28]Perl M,Lomas-Neira J,Chung CS.Acute Lung Injury:Neutrophils,Epithelial Cell Death & Inflammation:A Unifying Hypothesis.Mol Med,2008,Articles Published Online First.
[29]Lomas-Neira JL,Chung CS,Wesche DE,et al.In vivo gene silencing(with siRNA)of pulmonary expression of MIP-2 versus KC results in divergent effects on hemorrhage-induced,neutrophil-mediated septic acute lung injury J Leukoc Biol,2005,77(6):846-53.
[30]Lau D,Mollnau H,Eiserich JP,et al.Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins.Proc Natl Acad Sci USA,2005,102:431-36.
[31]Seymour J.Klebanoff.Myeloperoxidase:friend and foe.Journal of Leukocyte Biology,2005,77:598-625.
[32]Nys M,Preiser JC,Deby-Dupont G,et al.Nitric oxide-related products and myeloperoxidase in bronchoalveolar lavage fluids from patients with ALI activate NF-kappa B in alveolar cells and monocytes.Vascul Pharmacol,2005,43(6):425-33.
[33]Suratt BT,Parsons PE.Mechanisms of acute lung injury/acute respiratory distress syndrome.Clin Chest Med,2006,27(4):579-89.
[34]Calfee CS,Matthay MA:Nonventilatory treatments for acute lung injury and ARDS.Chest,2007,131:913-20.
[35]Spragg RG;Lewis JF,Walmrath HD,et al.Effect of recombinant surfactant protein C-based surfactant on the acute respiratory distress syndrome.N Engl J Med,2004,351:884-92.
[36]Rossaint R,Falke KJ,Lopez F,et al.Inhaled nitric oxide for the adult respiratory distress syndrome.N Engl J Med,1998,328:399-405.
[37]Slotman GJ,Burchard KW,D'Arezzo A,et al.Ketoconazole prevents acute respiratory failure in critically ill surgical patients.J Trauma,1988,28:648-54.
[38]Sprung CL,Caralis PV,Marcial EH,et al.The effects of highdose corticosteroids in patients with septic shock.A prospective,controlled study.N En Med,1984,311:1137-1143.
[39]Wiedemann HP,Arroliga AC,Komara J,et al.The Acute Respiratory Distress Syndrome Network:Randomized,placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome.Crit Care Med,2002,30(1):1-6.
[40]Ito K,Mizutani A,Kira S,et al.Effect of Ulinastatin,a human urinary trypsin inhibitor,on the oleic acidinduced acute lung injury in rats via the inhibition of activated leukocytes.Injury,2005,36(3),387-394.
[41]Ridsdale R,Tseu I,Roth-Kleiner M,et al.Increased phosphatidylcholine production but disrupted glycogen metabolism in fetal type Ⅱ cells of mice that overexpress CTP:phosphocholine cytidylyltransferase.J Biol Chem,2004,279(53):55946-57.
[42]Zhou J,Ryan AJ,Medh J,et al.Oxidized lipoproteins inhibit surfactant phospha tidylcholine synthesis via calpain-mediated cleavage of CTP:Phosphorcholine cytidylyltransferase.J Biol Chem,2003,278(39):37032-40.
[43]Mallapalli RK,Ryan AJ,Salome RG,et al.Tumor necrosis factor-alpha inhibits expression of CTP:phosphocholine cytidylyltransferase.J Biol Chem,2000,275(13):9699-708
[44]Sun Y,Wang YQ,Zhong JG,et al.Influence of porcine pulmonary surfactant administered at different time on therapeutic effects in rats with oleic acid induced acute lung injury.Zhongguo Wei Zhong Bing Ji Jiu Yi Xue,2008,20(2):88-91.
[45]崔社怀,郭先健。急性低氧油酸肺损伤表面活性物质相关蛋白表达的变化。中华结核和呼吸感染,1998,2(24):89-93.
[46]Rosemary B.Comell,,Ingrid C.Northwood.Regulation of CTP:phosphocholine cytidylyltransferase by amphitropism and relocalization.TIBS,2000,25:441-447.
[47]Ross Ridsdale,Irene Tseu,Jinxia Wang,etal.CTP:Phosphocholine Cytidylyltransferaseα Is a Cytosolic Protein in Pulmonary Epithelial Cells and Tissues.J Biol Chem.2001,276(52):49148-49155.
[48]Sugimoto H,Banchio C,Vance DE.Transcriptional regulation of phosphatidylcholine biosynthesis. Prog Lipid Res, 2008, 6:204-20.
[49] Karim M, Jackson P, Jackowski SMol. Gene structure, expression and identification of a new CTP: phosphocholine cytidylyltransferase beta isofonn, Biochim Biophys Acta, 2003, 1633(1): 1-12.
[50] Sugimoto H, Okamura K, Sugimoto S, et al. Sp1 is a co-activator with Ets-1, and Net is an important repressor of the transcription of CTP:phosphocholine cytidylyltransferase alpha. J Biol Chem, 2005,280(49):40857-66.
[51] Banchio C, Lingrell S, Vance DE. Sp-1 binds promoter elements that are regulated by retinoblastoma and regulate CTP:phosphocholine cytidylyltransferase-alpha transcription.J Biol Chem, 2007,282(20):14827-35.
[52] Bakovic M, Waite KA, Vance DE. Functional significance of Spl, Sp2, and Sp3 transcription factors in regulation of the murine CTP:phosphocholine cytidylyltransferase alpha promoter. J Lipid Res, 2000, 41(4):583-94.
[53] Bouwman P, Philipsen S. Regulation of the activity of Sp1-related transcription factors. Mol Cell Endocrinol., 2002, 195(1-2): 27-38.
[54] Zhou JM, You Y, Zabner J, et al. The CCT Promoter Directs High-Level Transgene Expression in Distal Lung Epithelial Cell Lines. Am J Respir Cell Mol Biol, 2004, 30: 61-68
[55] Jie Wan, Brian A. Carr, N. Shane Cutler, et al. Spl and Sp3 regulate basal transcription of the human CYP2F1 gene.Drug Metabolish and Disposition, 2005, 30(8):1244-1253.
[56] Zhao C, Meng A. Sp1-like transcription factors are regulators of embryonic development in vertebrates. Dev Growth Differ, 2005, 47(4): 201-11.
[57] GSuske. The Sp-family of transcription factors. Gene, 1999, 238:291-300.
[58] Li L, He SH, Sun JM, et al. Gene regulation by Spl and Sp3. Biochemistry and Cell Biology, 2005, 82: 460-71.
[59] Rickers A, Peters N, Badock V, et al. Cleavage of transcription factor SP1 by caspases during anti-IgM-induced B-cell apoptosis. J Biochem, 1999, 261:269-74.
[60] Chu S, Ferro TJ. Sp1: regulation of gene expression by phosphorylation. Gene, 2005, 348(1): 1-11.
[61] Sugimoto H, Banchio C, Vance DE. Transcriptional regulation of phosphatidylcholine biosynthesis.Progress in Lipid Research, 2008, 47 : 204-20.
[62] Banchio C, Schang LM, Vance DE. Phosphorylation of Spl by cyclin-dependent kinase 2 modulates the role of Spl in CTP:phosphocholine cytidylyltransferase alpha regulation during the S phase of the cell cycle. J Biol Chem., 2004,279(38):40220-6.
[63] Banchio C, Schang LM, Vance DE. Activation of CTP: phosphocholine cytidylyltransferase alpha expression during the S phase of the cell cycle is mediated by the transcription factor Spl. J Biol Chem.2003, 278(34): 32457-64.
[1]Clement JM,Kent C.CTP:phosphocholine cytidylyltransferase:insights into regulatory mechanisms and novel functions.Biochem Biophys Res Commun,1999,257(3):643-50.
[2]Waite K,Tang W,Tabas I,et al.Transcriptional activation of the murine CTP:phosphocholine cytidylyltransferase gene(Ctpct):combined action of upstream stimulatory and inhibitory cis-acting elements.Biochim Biophys Acta,1999,1438(1):147-65.
[3]Lykidis A,Murti KG,Jackowski S.Cloning and characterization of a second human CTP:phosphocholine cytidylyltransferase.J Biol Chem,1998,273(22):14022-9.
[4]Karim M,Jackson P,Jackowski S.Gene structure,expression and identification of a new CTP:phosphocholine cytidylyltransferase beta isoform.Biochim Biophys Acta,2003,1633(1):1-12.
[5]Ridsdale R,Tseu I,Wang J,et al.CTP:phosphocholine cytidylyltransferase alpha is a cytosolic protein in pulmonary epithelial cells and tissues.J Biol Chem,2001,276(52):49148-55.
[6]DeLong C J,Qin L,Cui Z.Nuclear localization of enzymatically active green fluorescent protein-CTP:phosphocholine cytidylyltransferase alpha fusion protein is independent of cell cycle conditions and cell types.J Biol Chem,2000,275(41):32325-30
[7]Rosemary B.Cornell,Ingrid C.Northwood.Regulation of CTP:phosphor-choline cytidylyltransferase by amphitropism and relocalization.Trends in Biochemical Sciences,2000,25(9):441-447.
[8]Joel M.Clement and Claudia Kent.CTP:Phosphocholine Cytidylyltransferase:Insights into Regulatory Mechanisms and Novel Functions.Biochemical and Biophysical Research Communications,1999,257:643-650.
[9]Wang L,Magdaleno S,Tabas I,et al.Early embryonic lethality in mice with targeted deletion of the CTP:phosphocholine cytidylyltransferase alpha gene (Pcytla).Mol Cell Biol,2005,25(8):3357-63.
[10]罗自强,冯丹丹,周伏文。低浓度内皮素-1对活性氧抑制肺表面活性物质脂质合成的保护,生理学报,2002,2(54):89-93.
[11]Tian Y,Zhou R,Rehg JE.Role of phosphocholine cytidylyltransferase alpha in lung development.Mol Cell Biol.2007,7(3):975-82.
[12]Zhou JM,You Y,J Zabner,et al.The CCT Promoter Directs High-Level Transgene Expression in Distal Lung Epithelial Cell Lines.Am J Respir Cell Mol Biol,2004,30(1):61.
[13]Zuo YY,Veldhuizen RA,Neumann AW,et al.Current perspectives in pulmonary surfactant - Inhibition,enhancement and evaluation.Biochimica et Biophysica Acta,2008,Epub ahead of print.
[14]A.Gunther,R.Schmidt,J.Harodt,T,et al.Bronchoscopic administration of bovine natural surfactant in ARDS and septic shock:impact on biophysical and biochemical surfactant properties.Eur Respir J,2002,19:797-804.
[15]Odalys Blanco,Jesus Pérez-Gil.Biochemical and pharmacological differences between preparations ofexogenous natural surfactant used to treat Respiratory Distress Syndrome:Role of the different components in an efficient pulmonnary surfactant.Eur J Pharm,2007,(568):1-15.
[16]Tian Y,Zhou R,Rehg JE,et al.Role of phosphocholine cytidylyltransferase alpha in lung development.Mol Cell Biol.2007,27(3):975-82.
[17]McCoy DM,Fisher K,Robichaud J,et al.Transcriptional regulation of lung cytidylyltransferase in developing transgenic mice.Am J Respir Cell Mol Biol.2006,35(3):394-402.
[18]Vivekananda J,Smith D,King RJ.Sphingomyelin metabolites inhibit sphingomyelin synthase and CTP:phosphocholine cytidylyltransferase.Am J Physiol Lung Cell Mol Physiol,2001,281(1):98-107.
[19]Choline Deficiency Causes Translocation of CTP:Phosphocline Cytidyltansferase from Cytosol to Endoplasmic Reticulumn in Rat Liver.J Biol Chem.200,265(8):1 62-8.
[20]Suzanne Jackowski,Paolo Fagone.CTP:Phosphocholine Cytidylyltransferase:Paving the Way from Gene to Membrane.J Biol Chem.2005,280(2):853-6.
[21]龚小慧,胡肖伟,孙波。吸人一氧化氮对内毒素性肺损伤大鼠肺磷脂合成的影响。中华急诊医学杂志,2004,13(6):382-5.
[22]Li J,Marsh JJ,Spragg RG.Effect of CTP:phosphocholine cytidylyltransferase overexpression on the mouse lung surfactant system.Am J Respir Cell Mol Biol,2002,(6):709-15.
[23]Storey MK,Byers DM.Decreased phosphatidylcholine biosynthesis and abnormal distribution of CTP:phosphocholine cytidylyltransferase in cholesterol auxotrophic Chinese hamster ovary cells. J Lipid Res, 1997, (4):711-22.
[24] Jacobs RL, Lingrell S, Zhao Y, et al. Hepatic CTP:phosphocholine cytidylyltransferase-alpha is a critical predictor of plasma high density lipoprotein and very low density lipoprotein. J Biol Chem, 2008, 283(4): 2147-55.
[25] Mallampalli RK, Ryan AJ, Carroll, JL, et al. Lipid deprivation increases surfactant phosphatidylcholine synthesis via a sterol-sensitive regulatory element within the CTP:phosphocholine cytidylyltransferase promoter. Biochem J, 2002,362:81-88.
[26] Zhou J., Ryan AJ, Medh J, et al. Oxidized lipoproteins inhibit surfactant phosphatidylcholine synthesis via calpain-mediated cleavage of CPT:Phosphocholine cytidylyltransferasen. J Biol Chem, 2003, 278: 37032-40.
[27] Lagace TA, Miller JR, Ridgway ND. Caspase processing and nuclear export of CTP:phosphocholine cytidylyltransferase alpha during farnesol-induced apoptosis. Mol Cell Biol, 2002, 2(13):4851-62.
[28] Agassandian M, Zhou J, Tephly LA, et al. Oxysterols inhibit phosphatidylcholine synthesis via ERK docking and phosphorylation of CTP:phosphocholine cytidylyltransferase. J Biol Chem, 2005, 280(22):21577-87.
[29] Chen BB, Mallampalli RK.Calmodulin binds and stabilizes the regulatory enzyme, CTP: phosphocholine cytidylyltransferase. J Biol Chem. 2007,282 (46):33494-506
[30] Mallampalli. RK,Ryan AJ,Salome RG,et al. Tumor necrosis factor-alpha inhibits expression of CTP:phosphocholine cytidylyltransferase. J Biol Chem.2000, 275(13):9699-708.
[31] Kitos TE, Choi CM, Cornell RB. Angiotensin stimulates phosphatidylcholine synthesis via a pathway involving diacylglycerol, protein kinase C, ERK1/2, and CTP:phosphocholine cytidylyltransferase. Biochim Biophys Acta. 2006, 1761 (2):272-9.
[32] Wang Y, Kent C. Effects of altered phosphorylation sites on the properties of CTP: phosphocholine cytidylyltransferase. J Biol Chem, 1995, 270:17843-9.
[33] Jamil H, Utal AK, Vance DE. Evidence that cyclic AMP induced nhibition of phosphatidylcholine biosynthesis is caused by a decrease in cellular diacylglycerol levels in cultured rat hepatocytes.J Biol Chem,1992,267:1752-60.
[34]Shiratori Y,Houweling M,Zha X,Tabas I.Stimulation of CTP:phosphocholine cytidylyltransferase by free cholesterol loading of macrophages involves signaling through protein dephosphorylation.J Biol Chem.1995,270:29894-903.
[35]Mallampalli RK.Oxysterols inhibit phosphatidylcholine synthesisvia ERK docking and phosphorylation of CTP:phosphocholine cytidylyltransferase.J Biol Chem,2005,280:21577-87.
[36]Li L,Luo ZQ,Zhou FW,et al.Effect of vasoactive intestinal peptide on pulmonary surfactants phospholipid synthesis in lung explants.Acta Pharmacol Sin,2004,25(12):1652-8.
[37]McCoy DM,Fisher K,Robichaud J,Ryan AJ,Mallampalli RK.Transcriptional regulation of lung cytidylyltransferase in developing transgenic mice.Am J Respir Cell Mol Biol,2006,35(3):394-402.
[38]Sugimoto H.Transcriptional regulation of CTP:phosphocholine cytidylyltransferase in phospholipid biosynthesis.Seikagaku.2007,79(10):968-72.
[39]Sugimoto H,Banchio C,Vance DE.Transcriptional regulation of phosphatidylcholine biosynthesis.Prog Lipid Res,2008,47:204-220.
[40]Sugimoto H,Okamura K,Sugimoto S,et al.Sp1 is a co-activator with Ets-1,and Net is an important repressor of the transcription of CTP:phosphocholine cytidylyltransferase alpha.J Biol Chem.2005,280(49):40857-66.
[41]Bakovic M,Waite KA,Vance DE.Functional significance of Sp1,Sp2,and Sp3 transcription factors in regulation of the murine CTP:phosphocholine cytidylyltransferase alpha promoter.J Lipid Res.2000,41(4):583-94.
[42]薛丽香,翁默,吴军峰。Sp1和Sp3介导的转录调控。 中国生物化学与分子生物学报,2006,22(2):106-110.
[43]Claudia B,Luis M.S,Dennis EV.Activation of CTP:Phosphocholine Cytidylyltransferase Expression during the S Phase of the Cell Cycle Is Mediated by the Transcription Factor Sp1.J Biol Chem,2003,278(34):32457-64.
[44]Hiroyuki S,Marica B,Satoshi Y.Identification of Transcriptional Enhancer Factor-4 as a Transcriptional Modulator of CTP:Phosphocholin Cytidylyltransferase a. J Biol Chem, 2001, 276(15): 12338-44.
[45] Ridgway ND, Lagace TA. Regulation of the CDP-choline pathway by sterol regulatory element binding proteins involves transcriptional and post-transcriptional mechanisms. Biochem J, 2003, 372(3):811-9.
[46] Udvadia AJ, Templeton DJ, Horowitz JM. Functional interactions between the retinoblastoma (Rb) protein and Sp-family members: superactivation by Rb requires amino acids necessary for growth suppression. J Biol Chem. 2007, 282(20): 14827-35.
[47] Banchio C, Lingrell S, Vance DE. Sp-1 binds promoter elements that are regulated by retinoblastoma and regulate CTP:phosphocholine cytidylyltransferase-alpha transcription. J Biol Chem, 2007,282(20):14827-35.
[48] Tseu I, Ridsdale R, Liu J, et al. Cell cycle regulation of pulmonary phosphatidylcholine synthesis. Am J Respir Cell Mol Biol. 2002, 26(4):506-15.
[49] Jackowski S. Coordination of membrane Phospholipid synthesis with the cell cycle. J Biol Chem.1994, 269(5):3858-67.
[50] Golfman LS,Bakovic M, Vance DE.Transcription of the CTP:phosphocholine cytidylyltransferase alpha gene is enhanced during the S phase of the cell cycle. J Biol Chem. 2001, 76 (47):43688-92.
[51] Suzanne Jackowski .Cell Cycle Regulation of Membrane Phospholipid Metabolism. J Biol Chem. 1996, 271(34): 20219-22.
[52] Banchio C, Schang LM, Vance DE. Phosphorylation of Sp1 by cyclin-dependent kinase 2 modulates the role of Spl in CTP: phosphocholine cytidylyltransferase alpha regulation during the S phase of the cell cycle. J Biol Chem. 2004, 279 (38):40220-6.
[53] Tseu I, Ridsdale R, Liu J, Wang J, et al. Cell cycle regulation of pulmonary phosphatidylcholine synthesis.J Respir Cell Mol Biol, 2002, 26:506-15.
[54] Sewack G F, Elis T W, Hansen U. Binding of TATA binding Protein to a naturally positioned nucleosome is facilitated by histone acetylation. Mol Ceil Biol, 2001, 21: 1404-15
[55] KouzaridesT. Histone acetylases and deacetylases in ceil proliferation. Curr Opin Genet Dev, 1999, 9: 40-8.
[56] Cheng M, Olivier P, Diehl J A, et al. The p21(Cipl) and p27(Kip1) CDK 'inhibitors' are essential activators of cyclin D-dependent kinases in murine fibroblasts. EMBO J, 1999, 18(6): 1571-1583.
[57] Vigushini D M, Coombes R C. Histone Deacetylase inhibitors in cancer treatment. Anticancer Drugs, 2002, 13(1): 1-13
[58] Banchio C, Lingrell S, Vance DE. Role of histone deacetylase in the expression of CTP:phosphocholine cytidylyltransferase alpha. J Biol Chem, 2006,281:10010-5.
[59] Doetzlhofer A, Rotheneder H, Lagger G, et al. Histone deacetylase 1 can repress transcription by binding to Sp1. Mol Cell Biol, 1999,19:5504-11.
[60] Liu H, Dibling B, Spike B,et al. New roles for the RB tumor suppressor protein.Curr Opin Genet.Dev, 2004,4:55-64.
[61] Banchio C, Lingrell S, Vance DE. Sp-1 binds promoter elements that are regulated by Rb and regulate CTP: phosphocholine cytidylyltransferase-alpha transcription. Biol Chem, 2007, 282:14827-45.