title: Involvement of p38 mitogen-activated protein kinase and apoptosis signal-regulating kinase-1 in nitric oxide-induced cell death in PC12 cells.
abstract: Although nitric oxide (NO) plays key signaling roles in the nervous systems, excess NO leads to cell death. In this study, the involvement of p38 mitogen-activated protein kinase (p38 MAPK) and apoptosis signal-regulating kinase-1 (ASK1) in NO-induced cell death was investigated in PC12 cells. NO donor transiently activated p38 MAPK in the wild type parental PC12 cells, whereas the p38 MAPK activation was abolished in NO-resistant PC12 cells (PC 12-NO-R). p38 MAPK inhibitors protected the cells against NO-induced death, whereas the inhibitors were not significantly protective against the cytotoxicity of reactive oxygen species. Stable transfection with dominant negative p38 MAPK mutant reduced NO-induced cell death. Stable transfection with dominant negative mutant of ASK1 attenuated NO-stimulated activation of p38 MAPK and decreased NO-induced cell death. These results suggest that p38 MAPK and its upstream regulator ASK1 are involved in NO-induced PC12 cell death.
authors.affiliation: Department of Biochemistry, College of Medicine, Chung-Ang University, Seoul, Korea.
authors.forename: O J
authors.initials: OJ
authors.lastname: Han
authors.forename: K H
authors.initials: KH
authors.lastname: Joe
authors.forename: S W
authors.initials: SW
authors.lastname: Kim
authors.forename: H S
authors.initials: HS
authors.lastname: Lee
authors.forename: N S
authors.initials: NS
authors.lastname: Kwon
authors.forename: K J
authors.initials: KJ
authors.lastname: Baek
authors.forename: H Y
authors.initials: HY
authors.lastname: Yun
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004351:Drug Resistance; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005799:Genes, Dominant; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects; D010766:Phosphorylation; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases