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PKC上调心脏营养素-1促进心肌细胞的存活率(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2006年第4期
页码:
406-410
栏目:
基础研究
出版日期:
2006-08-25

文章信息/Info

Title:
Protein kinase C upregulates survival rate of cardiotrophin-1-induced cardiac myocytes
作者:
符史干; 董战玲; 翁启芳; 许闽广; 周升; 谢协驹
海南医学院生理学教研室，海南 海口 571101
Author(s):
FU Shi-gan;  DONG Zhan-ling;  WENG Qi-fang;  XU Min-guang;  ZHOU Sheng;  XIE Xie-ju
Department of Physiology, Hainan Medical College, Haikou,Hainan 571101, China
关键词:
心肌细胞培养; 心脏营养素1; 蛋白激酶C; 丝裂原激活蛋白激酶; 存活率
Keywords:
neonatal rat myocardial cell culture;  cardiotrophin1;  protein kinase C;  mitogenactivated protein kinase; survival rate
分类号:
Q463;R331.36
DOI:
-
文献标识码:
A
摘要:
目的 观察心脏营养素-1（CT-1）对培养乳鼠心肌细胞存活率的影响以及蛋白激酶C（PKC）信号转导通路在调控CT-1诱导心肌细胞存活中的作用。方法 分离、纯化并差速贴壁培养新生大鼠心肌细胞，MTT比色法测定各孔心肌细胞存活率。结果 ①无血清DMEM培养心肌细胞24 h后加入4个剂量组CT-1 (0.1～10 nmol/L)，随着剂量的增加MTT计数随之增高，呈明显的剂量依赖性；②在培养介质中预先加入蛋白激酶 C（PKC）激动剂佛波酯（PMA），30 min后再加入CT-1，MTT计数明显增加，而用PKC抑制剂Calphostin C（Cal）则使MTT计数明显降低；③用丝裂原激活蛋白激酶（MAPK）亚型细胞外信号调节激酶（ERK）选择性抑制剂PD098059进行预处理，再加入CT1，心肌细胞存活率明显降低，与单纯CT-1组相比有显著性差异；单纯用ERK抑制剂PD098059对心肌细胞存活率无明显影响；预先加入ERK抑制剂PD098059，再加入PMA和CT-1，MTT计数明显降低，与（PMA＋CT-1）组相比有极显著性差异。结论 CT-1对心肌细胞存活率具有明显的剂量依赖性；PKC可上调CT-1促进的心肌细胞存活率，PKC可能成为CT1促进心肌细胞存活率的信号转导通路之一；CT-1诱导心肌细胞存活率的胞内信号转导通路可能是先激活PKC，然后诱导MAPK亚型ERK的激活。
Abstract:
AIM To observe the effects of cardiotrophin-1(CT-1), an interleukin 6related cytokine, on the survival rate of cultured neonatal rat myocardial cell and the effects of protein kinase C（PKC）signal transduction pathway in regulating the survival rate of CT-1-induced cells. METHODS The cardiomyocytes of neonatal rats were isolated, purified and cultured with method of preplating for different times and the cell survival rate of each well was measured with MTT chromatometry approach. RESULTS ①The survival rate of cardiac myocytes increased by CT1 in a dosedependent manner (0.1-10 nmol/L) in cultured neonatal rat cardiomyocytes. ②This effect was strengthened by the phorbol 12myristate 13acetate (PMA,10 μmol/L), a PKC activator. In contrast, pretreatment of Calphostin C (Cal,10 μmol/L), a PKC inhibitor, significantly decreased the survival rate of CT-1induced cardiac myocytes. ③The pretreatment of PD098059（50 μmol/L）, a mitogenactivated protein kinase (MAPK,ERK1/2）specific blocker, also significantly decreased the survival rate of cardiomyocytes promoted by CT-1 and abolished the effect of PMA on CT-1induced cardiac myocytes survival in vitro. CONCLUSION CT-1 is a potent factor of promoting myocardial survival and significantly increases the survival rate of cardiomyocytes in a dosedependent manner in cultured myocardial cells of neonatal rats. PKC can upregulate CT-1induced myocardial survival. MAPK signaling transduction pathway may be a downstream target site of PKC signaling molecule in CT1 induced cardiomyocyte survival in vivo.

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备注/Memo

备注/Memo:
收稿日期：2005-12-12.基金项目：国家自然科学基金项目资助（No.30260032） 通讯作者：符史干，教授,主要从事心血管生理学研究 Tel：（0898）66893740 Email：fushigan@yahoo.com.cn
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