JNK and p38 MAPK regulate oxidative stress and the inflammatory response in chlorpyrifos-induced apoptosis

Abstract

To investigate mechanisms of neuronal cell death in response to chlorpyrifos (CPF), a pesticide, we evaluated the regulation of ROS and COX-2 in human neuroblastoma SH-SY5Y cells treated with CPF. CPF treatment produced cytotoxic effects that appeared to involve an increase in ROS. In addition, CPF treatment activated MAPK pathways including JNK, ERK1/2, and p38 MAPK, and MAPK inhibitors abolished the cytotoxicity and reduced ROS generation. Our data demonstrate that CPF induced apoptosis involving MAPK activation through ROS production. Furthermore, after the CPF treatment, COX-2 expression increased. Interestingly, JNK and p38 MAPK inhibitors attenuated the CPF-induced COX-2 expression while an ERK1/2 inhibitor did not. These findings suggest that pathways involving JNK and p38 MAPK, but not ERK1/2, mediated apoptosis and are involved in the inflammatory response. In conclusion, the JNK and p38 MAPK pathways might be critical mediators in CPF-induced neuronal apoptosis by both generating ROS and up-regulating COX-2. Crown Copyright (c) 2013 Published by Elsevier Ireland Ltd. All rights reserved.This work was supported by the Korea Science and Engineering Foundation (2011-0028269) through the Medical Research Center at Hanyang University College of Medicine, Republic of Korea, and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0026926)