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阻断p38信号转导通路对血管平滑肌细胞增殖和凋亡的影响(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2011年第5期
页码:
579-583
栏目:
基础研究
出版日期:
2011-10-25

文章信息/Info

Title:
Molecular mechanism of p38 signaling pathway regulation for proliferation and apoptosis of rat vascular smooth muscle cells
作者:
唐 梅王翠英李 敏
首都医科大学附属北京友谊医院综合内科
Author(s):
TANG Mei WANG Cui-ying LI Min
Department of Comprehensive Internal Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
关键词:
血管平滑肌细胞p38有丝分裂原激活的蛋白激酶抑制剂大鼠
Keywords:
vascular smooth muscle cell p38 mitogen-activated protein kinase inhibitor proliferation apoptosis
分类号:
Q555.7
DOI:
-
文献标识码:
A
摘要:
目的:研究老年大鼠血管平滑肌细胞(VSMCs)增殖和凋亡与p38信号转导通路的关系,明确以p38为靶向的信号转导在VSMCs中的分子调控机制。方法: 将p38特异性抑制剂SB203580(25 μmol/L)作用于大鼠VSMCs,运用MTT比色法检测细胞增殖状态,流式细胞术检测SB203580对细胞凋亡的影响,Western blot法检测药物作用前后p38通路相关蛋白p38α、MKK3、GADD153和c-myc的表达及相关蛋白磷酸化活性。结果: SB203580可以时间、剂量依赖的方式抑制VSMCs增殖促进其凋亡。加入SB203580的VSMCs中p-p38α、GADD153和c-myc表达的水平,随作用时间的延长而下降(P<0.01)。结论: 阻断p38信号转导通路可能通过下调其下游靶基因GADD153和C-myc的表达,抑制血管平滑肌细胞增殖,促进其凋亡。
Abstract:
AIM:To investigate the relationship between p38 signal transduction pathway and the proliferation and apoptosis of vascular smooth muscle cells (VSMCs) in rats of old age and to establish a mechanism of p38-targeted treatment for VSMCs. METHODS: Rat VSMCs were treated with SB203580 (a selective p38 inhibitor). MTT assay and flow cytometry were used to measure proliferation and apoptosis. Expressions of p-p38, MKK3, GADD153 and C-myc proteins were measured by Western blot. RESULTS: SB203580 inhibited cell proliferation, induced apoptosis in a dose- and time-dependent manner and resulted in a significant downregulation of p-p38, GADD153 and C-myc (P<0.01). CONCLUSION: Our results show that blocked p38 signaling pathway induces apoptosis and inhibits proliferation of VSMC through decreasing the GADD153 and C-myc expression of p38 downstream target genes.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期:2010-09-15.基金资助:北京市自然科学基金资助(7112033) 通讯作者:李敏,主任医师,主要从事老年心血管病临床与基础研究Email:limin55122@hotmail.com 作者简介:唐梅,副主任医师,硕士生Email:tangmei125@126.com
更新日期/Last Update: 2011-11-03