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Essential role of p38 MAPK in caspase‐independent, iPLA 2 ‐dependent cell death under hypoxia/low glucose conditions
Author(s) -
Aoto Mamoru,
Shinzawa Koei,
Suzuki Yoji,
Ohkubo Nobutaka,
Mitsuda Noriaki,
Tsujimoto Yoshihide
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.04.028
Subject(s) - p38 mitogen activated protein kinases , hypoxia (environmental) , programmed cell death , apoptosis , microbiology and biotechnology , protein kinase a , reactive oxygen species , mapk/erk pathway , chemistry , kinase , biology , biochemistry , oxygen , organic chemistry
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.