Effect of PP60c-Src on Ang Ⅱ- induced signal transduction in rat vascular smooth muscle cells
- VernacularTitle:PP60c-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
- Author:
Meixiang XIANG
;
Dong LIU
- Publication Type:Journal Article
- Keywords:
Muscle,smooth,vascular;
Angiotensin Ⅱ;
c- Src;
c- Fos;
Mitogen- activated protein kinases
- From:
Chinese Journal of Pathophysiology
2005;21(4):685-689
- CountryChina
- Language:Chinese
-
Abstract:
AIM: The aim of the present study was to clarify the mechanism of intracellular signal transduction in Ang Ⅱ- induced proliferation 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 with 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 protein expression. c- Src kinase activity was measured by protein immunoprecipitation and kinase autophosphorylation. The phosphorylation rate of the substrate myelin basic protein (MBP) was employed to assess MAPK activity.Western immunoblot was used to detect protein expression of c- Src and c-Fos. RESULTS: c-Src protein expression in VSMC transfected with different concentrations of anti- sense ODNs significantly decreased in a negative dose- effect manner. c- Src kinase activity was also markedly inhibited. Following the 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 findings indicate that c- Src is an important signal factor in Ang Ⅱ-induced VSMC proliferation.
