| PP~(60c-Src)在血管紧张素II诱导的大鼠血管平滑肌细胞信息转导中的作用(英文) |
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| 引用本文： | 项美香,刘东. PP~(60c-Src)在血管紧张素II诱导的大鼠血管平滑肌细胞信息转导中的作用(英文)[J]. 中国病理生理杂志, 2005, 0(4) |
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| 作者姓名： | 项美香 刘东 |
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| 作者单位： | 浙江大学医学院附属二院心内科 浙江杭州310009(项美香)，浙江大学医学院附属二院心内科 浙江杭州310009(刘东) |
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| 基金项目： | SupportedbytheFoundationofNationalNaturalScience (No.39370 319) |
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| 摘 要： | 目的:本研究通过观察c -Src在AngII对大鼠血管平滑肌细胞(VSMC)丝裂原激活的蛋白激酶(MAPK)的激活和c -Fos蛋白表达中的影响,以进一步阐明AngII促VSMC增殖的细胞内信息转导机制。方法:原代和传代培养SD大鼠主动脉VSMC ,以脂质体包裹反义c -Src寡脱氧核苷酸(oligodeoxynucleotides,ODNs)转染培养的VSMC以抑制c -Src蛋白表达和激酶活性。以未转染的VSMC为对照,观察10 -7mol/LAngII刺激对转染的VSMC的MAPK活性和c -Fos蛋白表达的影响。蛋白免疫沉淀和酶自身磷酸化率法测定c -Src激酶活性;髓鞘碱性蛋白(MBP)底物磷酸化率测定MAPK激酶活性;Westernblotting免疫印迹法测定c-Src和c -Fos蛋白表达情况。结果:转染不同浓度反义c-SrcODNs的VSMC ,c -Src蛋白含量呈浓度依赖性降低,c-Src激酶活性也显著抑制,以AngII刺激经转染反义c -SrcODNs的VSMC ,c -Src激酶活性增幅仅为对照组的8 .7% ;MAPK活性仅为对照的1 .6 % ;c -Fos蛋白表达的增幅为对照组的30 .0 %。结论:AngII可诱导VSMCc -Src激活和细胞内信息转导,且AngII引起的MAPK和c -fos的激活依赖于c-Src的激活,提示c -Src是AngII促血管平滑肌细胞增殖的重要信息分子。
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| 关 键 词： | 肌 平滑 血管 血管紧张素II c-Src c-Fos 有丝分裂素激活蛋白激酶类 |
Effect of PP~(60c-Src) on Ang II- induced signal transduction in rat vascular smooth muscle cells* |
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| XIANG Mei-xiang,LIU Dong. Effect of PP~(60c-Src) on Ang II- induced signal transduction in rat vascular smooth muscle cells*[J]. Chinese Journal of Pathophysiology, 2005, 0(4) |
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| Authors: | XIANG Mei-xiang LIU Dong |
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| Abstract: | AIM: The aim of the present study was to clar ify the mechanism of intracellular signal transduction in Ang II-induced prolife ration of vascular smooth muscular cells (VSMC) by observing the effect of c-Src on Ang II-mediated mitogen-activated protein kinase (MAPK) activation and c-Fos protein expression in cultured VSMC of rats. METHODS: Cultured aortic VSMCs from SD rats were transfected wit h anti-sense c-Src oligodeoxynucleotides (ODNs) wrapt with lipofectin to inhibit c-Src activity and protein production. Untransfected VSMCs were used as control . We observed the role of Ang II stimulation in MAPK activation and c-Fos protei n expression. c-Src kinase activity was measured by protein immunoprecipitation and kinase autophosphorylation. The phosphorylation rate of the substrate myeli n basic protein (MBP) was employed to assess MAPK activity. Western immunoblot w as used to detect protein expression of c-Src and c-Fos. RESULTS: c-Src protein expression in VSMC transfected with diffe rent concentrations of anti-sense ODNs significantly decreased in a negative dos e-effect manner. c-Src kinase activity was also markedly inhibited . Following t he stimulation of Ang II on transfected VSMCs with anti-sense ODNs, the increase rate of c-Src activity was 8.7% of that in control, the activity of MAPK was 1 .6% compared with control and c-Fos protein expression was as 30.0% as that of control. CONCLUSION: Ang II induces c-Src activation. MAPK activation and c-Fos protein expression by Ang II is dependent on c-Src activation. These find ings indicate that c-Src is an important signal factor in Ang II -induced VSMC proliferati on. |
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| Keywords: | Muscle smooth vascular Angiotensin II c-S rc c-Fos Mitogen-activated protein kinases |
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