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钙调神经磷酸信号通路参与心肌成纤维细胞的增殖(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2002年第3期
页码:
181-183
栏目:
实验研究
出版日期:
2002-05-01

文章信息/Info

Title:
Calcineurin signaling pathway involved in cultured rat cardiac fibroblasts proliferation
作者:
周兴文;  杨永健;  张　鑫;  朱　峻;  李　刚
成都军区成都总医院心血管内科, 四川 成都 610083
Author(s):
ZHOU Xing-wen;  YANG Yong-jian;  ZHANG Xin;  ZHU Jun; LI Gang
Department of Cardiology, General Hospital of Chengdu Army, Chengdu, Sichuan 610083, China
关键词:
钙调神经磷酸酶;  成纤维细胞;  心脏;  细胞增殖;  信号通路;  三磷酸肌醇;  环孢素A;  维拉帕米
Keywords:
cacineurin;  fibroblasts;  cardiac;  signaling pathway;  inositol (1;  4;  5)-trisphosphate;  cy-closporing A: verapamil;  cell proliferation
分类号:
Q813　
DOI:
-
文献标识码:
A
摘要:
目的 探讨钙调神经磷酸酶(CaN)依赖的信号通路在三磷酸肌醇(IP3)刺激的乳鼠心肌成纤维细胞(FBs) 增殖中的作用。方法 以培养的FBs为模型, 用IP3刺激FBs 内Ca2+释放, 环孢素A(CsA) 阻断CaN,维拉帕米(Ver)阻断FBs钙通道,检测FBs CaN丝裂素活化蛋白激酶(MAPK)、蛋白激酶C(PKC) 活性, 用3H2亮氨酸及3H2胸腺嘧啶掺入量作为反映FBs 增殖的指标。结果 IP3刺激组FBs蛋白核酸合成速率明显增高, 与对照组相比差异显著(P<0.01);CsA及Ver 能明显抑制IP3介导的FBs蛋白核酸合成速率增高, 与IP3刺激组相比差异显著(P< 0.01)。同时发现IP3刺激组CaN、PKC活性与对照FBs相比差异显著(P<0.05 或P<0.01)。CsA和Ver抑制IP3介导的FBs CaN活性增高,Ver抑制IP3介导的FBs PKC活性的增高。结论 CaN 在IP3刺激的FBs增殖中起重要作用,其它信号通路可能也参与了IP3刺激的FBs增殖。
Abstract:
AIM To study the effect of calcineurin (CaN)-dependent signaling passway on proliferation of rat cardiac fibroblasts(FBs) under stimulation of inositol(1,4,5)-trisphosphate(IP3).METHODS On the model of cultured rat FBs,Ca2+influx was stimulated with IP3;CaN signaling pathway was blocked with cyclosporine A(CsA) and Ca2+channel with verapamil (Ver),so as to detect the activities of FBs CaN,mitogen activated protein kinase (MAPK) and protein kinase C(PKC),3H-Leucine(3H-Leu) and3H-Thymidine(3H-TdR) incorporation was used as the target to evaluate FBs proliferation.RESUTLS Synthesis rates of protein and nucleic acid stimulated by IP3in FBs increased significantly in contrast to the control(P<0.01);CsA and Ver markedly inhibited the syntheses of protein and nucleic acid mediated by IP3in FBs with a significant difference from IP3-stimulated group (P<0.01). CsA and Ver also suppressed FBs CaN activity mediated by IP3,and Ver suppressed FBs PKC activity mediated by IP3.CONCLUSION CaN signaling pathway plays an important role in FBs proliferation induced by IP3, and other signaling pathways may be involved in FBs proliferation induced by IP3。

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备注/Memo

备注/Memo:
收稿日期：2001-08-06.基金项目: 四川省科委资助项目(2000145)
更新日期/Last Update: 2005-05-01