Essential role of p38 MAPK in caspase‐independent, iPLA 2 ‐dependent cell death under hypoxia/low glucose conditions

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.