Phospholipase C-gamma1 is required for cell survival in oxidative stress by protein kinase C.
Phospholipase C-gamma1 is required for cell survival in oxidative stress by protein kinase C.
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DOI：
10.1042/bj3630395
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发表时间：
2002-04
期刊：
影响因子：
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通讯作者：
X. Bai;F. Deng;An-ling Liu;Zhipeng Zou;Yu Wang;Zhi-yong Ke;Q. Ji;S. Luo
中科院分区：
文献类型：
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作者：
X. Bai;F. Deng;An-ling Liu;Zhipeng Zou;Yu Wang;Zhi-yong Ke;Q. Ji;S. Luo
磷脂酶C-Gamma1(PLC-Gamma1)的激活被报道在细胞对氧化应激的反应中提高细胞的存活率。我们利用PLC-Gamma1基因缺陷的小鼠胚胎成纤维细胞(PLCG1(-/-))及其野生型(PLCG1(+/+))，研究了蛋白激酶C(PKC)通路在氧化应激中介导PLC-Gamma1生存信号中的作用。H(2)O(2)以剂量和时间依赖的方式激活PLC-Gamma1。H(2)O(2)(1-5 mM)对两种细胞的PKC活性也有明显的促进作用，但在低剂量(50-200微米)时，PLCG1(-/-)细胞的PKC活性明显降低。与野生型细胞相比，经H(2)O(2)处理后，PLCG1(-/-)细胞的PKC依赖的Bcl2磷酸化水平和细胞存活率显著降低，caspase-3样活性显著升高。此外，用PKC特异性抑制剂处理PLCG1(+/+)细胞可降低PKC依赖的Bcl-2磷酸化水平，增强caspase-3活性，增强其对H(2)O(2)的敏感性。反之，用PKC特异性激活剂处理PLCG1(-/-)细胞后，细胞内Bcl2磷酸化水平升高，caspase-3活性降低，细胞存活率提高。这些结果表明，PLC-Gamma1通过PKC依赖的Bcl2的磷酸化和Caspase-3的抑制来介导氧化应激反应中的生存信号。
Phospholipase C-gamma1 (PLC-gamma1) activation has been reported to enhance cell survival during the cellular response to oxidative stress. We studied the role of protein kinase C (PKC) pathways in mediating PLC-gamma1 survival signalling in oxidative stress by using mouse embryonic fibroblasts genetically deficient in PLC-gamma1 (Plcg1(-/-)) and its wild type (Plcg1(+/+)). PLC-gamma1 was activated by H(2)O(2) treatment in a dose- and time-dependent manner. Activation of PKC was also markedly increased in both cell lines treated with H(2)O(2) (1-5 mM), but with low doses (50-200 microM), PKC activation was considerably decreased in Plcg1(-/-) cells. After treatment with H(2)O(2), PKC-dependent phosphorylation of Bcl-2 and cell viability of Plcg1(-/-) cells decreased dramatically and caspase-3-like activity increased significantly compared with that of the wild-type cells. Furthermore, pretreatment of Plcg1(+/+) cells with PKC-specific inhibitor decreased levels of PKC-dependent Bcl-2 phosphorylation, enhanced caspase-3 activity and their sensitivity to H(2)O(2). On the contrary, treatment of Plcg1(-/-) cells with PKC-specific activator increased the Bcl-2 phosphorylation, decreased caspase-3 activity and improved their survival. These results suggest that PLC-gamma1 mediates survival signalling in oxidative-stress response by PKC-dependent phosphorylation of Bcl-2 and inhibition of caspase-3.