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

Autor: Ki YW; Department of Pharmacology, College of Medicine, Hanyang University, 133-791 Seoul, Republic of Korea., Park JH, Lee JE, Shin IC, Koh HC
Jazyk: angličtina
Zdroj: Toxicology letters [Toxicol Lett] 2013 Apr 26; Vol. 218 (3), pp. 235-45. Date of Electronic Publication: 2013 Feb 14.
DOI: 10.1016/j.toxlet.2013.02.003
Abstrakt: 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 © 2013. Published by Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: