RRC ID 37755
著者 Aoto M, Shinzawa K, Suzuki Y, Ohkubo N, Mitsuda N, Tsujimoto Y.
タイトル Essential role of p38 MAPK in caspase-independent, iPLA(2)-dependent cell death under hypoxia/low glucose conditions.
ジャーナル FEBS Lett
Abstract 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.
巻・号 583(10)
ページ 1611-8
公開日 2009-5-19
DOI 10.1016/j.febslet.2009.04.028
PII S0014-5793(09)00311-1
PMID 19393651
MeSH Animals Caspases / metabolism* Cell Death / physiology Cell Hypoxia / physiology Cell Line, Tumor Glucose / metabolism Mice Phospholipases A2, Calcium-Independent / metabolism* Reactive Oxygen Species / metabolism Signal Transduction p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors p38 Mitogen-Activated Protein Kinases / metabolism*
IF 3.057
引用数 15
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞