Regulation of programmed cell death in neuronal cells by nitric oxide.
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.
Kang
Yun-Chul
YC
Vascular System Research Center and Department of Molecular and Cellular Biochemistry, College of Medicine, Kangwon National University, Chunchon, Kangwon-do, Korea.
Kim
Peter K
PK
Choi
Byoung-Min
BM
Chung
Hun-Taeg
HT
Ha
Kwon-Soo
KS
Kwon
Young-Guen
YG
Kim
Young-Myeong
YM
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*
D009569:Nitric Oxide; D020169:Caspases; D006152:Cyclic GMP