title: Regulation of programmed cell death in neuronal cells by nitric oxide.
abstract: Nitric oxide (NO), produced from L-arginine and molecular oxygen in a reaction catalyzed by one of three NO synthase isoenzymes, can prevent or induce neuronal apoptosis depending on its concentration and cellular redox state. This molecule affords neuroprotection by post-translational S-nitrosylation of NMDA receptor, caspases and p21ras, and increases the expression of cytoprotective genes such as HSP70, heme oxygenase and Bcl-2. Moreover, the NO/cGMP pathway activates the anti-apoptotic serine/threonine kinase Akt by protein kinase G-dependent activation of phosphatidylinositol 3-kinase. A high concentration of NO and peroxynitrite, a reaction product of NO with superoxide anion, can promote apoptotic pathways in neuronal cells through the indirect activation of caspases. We review the molecular mechanism by which NO exerts both pro- and anti-apoptotic actions in neuronal cells and the clinical implications for regulating neuronal apoptosis.
authors.affiliation: Vascular System Research Center and Department of Molecular and Cellular Biochemistry, College of Medicine, Kangwon National University, Chunchon, Kangwon-do, Korea.
authors.forename: Yun-Chul
authors.initials: YC
authors.lastname: Kang
authors.forename: Peter K
authors.initials: PK
authors.lastname: Kim
authors.forename: Byoung-Min
authors.initials: BM
authors.lastname: Choi
authors.forename: Hun-Taeg
authors.initials: HT
authors.lastname: Chung
authors.forename: Kwon-Soo
authors.initials: KS
authors.lastname: Ha
authors.forename: Young-Guen
authors.initials: YG
authors.lastname: Kwon
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; D020169:Caspases; D006152:Cyclic GMP