IGF I induction of p53 requires activation of MAP kinase in cardiac muscle cells.
IGF I induction of p53 requires activation of MAP kinase in cardiac muscle cells.
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IGF I 诱导 p53 需要激活心肌细胞中的 MAP 激酶。
DOI：
10.1006/bbrc.1998.8540
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Bahl,JJ
中科院分区：
文献类型：
--
作者：
Wang,PH;Schaaf,GJ;Chen,WH;Feng,J;Prins,BA;Levin,ER;Bahl,JJ
本研究的目的是探讨IGF I诱导p53表达和p21启动子是否需要激活心肌细胞中的MAP激酶。与对照载体转染的心肌细胞相比，在显性负性MAP激酶Y185转染的细胞中，IGF I对MAP激酶的激活降低了约60-70%。用Y185转染也导致IGF I对p53 mRNA的诱导减少（减少70%）。在用野生型p21 WAF 1/CIP 1启动子构建体转染的细胞中，在用Y185共转染的细胞中，IGF I对荧光素酶报告基因的激活减少。为了进一步证实这些发现，将细胞与特异性MAP激酶激酶抑制剂PD 98059预孵育。PD 98059抑制IGF I对p53 mRNA和p21 WAF 1/CIP 1启动子的诱导。这些结果表明IGF I对p53和p21 WAF 1/CIP 1的转录激活涉及心肌细胞中的MAP激酶通路，从而将MAP激酶与心肌细胞中细胞周期的负性调节联系起来。
The aim of this study was to investigate whether IGF I induction of p53 expression and p21 promoter require activation of MAP kinase in cardiac muscle cells. Compared to cardiomyocytes transfected with control vector, activation of MAP kinase by IGF I was decreased by approximately 60-70% in the cells transfected with dominant negative MAP kinase Y185. Transfection with Y185 also resulted in decreased induction of p53 mRNA by IGF I (70% reduction). In the cells transfected with a wildtype p21WAF1/CIP1promoter construct, activation of luciferase reporter gene by IGF I was decreased in the cells co-transfected with Y185. To further confirm these findings, cells were pre-incubated with PD98059, a specific MAP kinase kinase inhibitor. As expected, PD98059 inhibited induction of p53 mRNA and p21WAF1/CIP1promoter by IGF I. These data indicate that transcriptional activation of p53 and p21WAF1/CIP1by IGF I involves MAP kinase pathway in cardiomyocytes, and thus link MAP kinase to negative modulation of the cell cycle in cardiac muscle cells.