title: 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.
authors: Department of Pharmacology, College of Medicine, Hanyang University, 133-791 Seoul, Republic of Korea.
authors: Yeo-Woon
authors: YW
authors: Ki
authors: Jae Hyeon
authors: JH
authors: Park
authors: Jeong Eun
authors: JE
authors: Lee
authors: In Chul
authors: IC
authors: Shin
authors: Hyun Chul
authors: HC
authors: Koh
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004390:Chlorpyrifos / Q000633:toxicity*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007306:Insecticides / Q000633:toxicity*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D007306:Insecticides; D047428:Protein Kinase Inhibitors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D004390:Chlorpyrifos