Essential role of p38 MAPK in caspase-independent, iPLA2-dependent cell death under hypoxia/low glucose conditions
Essential role of p38 MAPK in caspase-independent, iPLA2-dependent cell death under hypoxia/low glucose conditions
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DOI：
10.1016/j.febslet.2009.04.028
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发表时间：
2009-05-19
期刊：
影响因子：
3.5
通讯作者：
Tsujimoto, Yoshihide
中科院分区：
文献类型：
--
作者：
Aoto, Mamoru;Shinzawa, Koei;Tsujimoto, Yoshihide
缺氧或缺血导致细胞死亡的机制尚不完全清楚。我们之前已经证明，缺氧诱导的细胞死亡独立于半胱天冬酶发生，并由磷脂酶A(2) （PLA(2)）介导。在这里，我们发现p38丝裂原激活的蛋白激酶在缺氧条件下被激活。p38的选择性抑制剂或p38 α蛋白水平的降低可防止缺氧诱导的细胞死亡。p38抑制剂可消除缺氧对PLA(2)的激活，表明p38作用于PLA(2)的上游。抗氧化剂n -乙酰半胱氨酸抑制p38的活化和缺氧诱导的细胞死亡，表明活性氧（ROS）参与了p38的活化。这些结果表明，ROS/p38/PLA(2)信号轴在缺氧诱导的caspase非依赖性细胞死亡中起着至关重要的作用。2009年，爱思唯尔b.v.代表欧洲生化学会联合会出版。版权所有。
The mechanisms of cell death induced by hypoxia or ischemia are not yet fully understood. We have previously demonstrated that cell death induced by hypoxia occurs independently of caspases, and is mediated by phospholipase A(2) (PLA(2)).Here, we show that p38 mitogen-activated protein kinase is activated under hypoxia. A selective inhibitor of p38 or decrease in the p38alpha protein level prevents hypoxia-induced cell death. The p38 inhibitor abolishes PLA(2) activation by hypoxia, indicating that p38 acts upstream of PLA(2). The antioxidant N-acetyl-cysteine inhibits activation of p38 and cell death induced by hypoxia, indicating that reactive oxygen species (ROS) are responsible for p38 activation. These results demonstrate that the ROS/p38/PLA(2) signaling axis has a crucial role in caspase-independent cell death induced by hypoxia. Crown Copyright (C) 2009 Published by Elsevier B. V. on behalf of Federation of European Biochemical society. All rights reserved.