Regulation of caspases by nitric oxide.
Nitric oxide can prevent or induce apoptosis depending on its concentration, cell type, and the oxidative milieu. Nitric oxide inhibits apoptosis and inflammation by S-nitrosylation of the active site cysteine of caspases, the central effector molecules of cell death as well as maturation of IL-1beta and IL-18. The ability of nitric oxide to S-nitrosylate caspases depends on multiple factors including the presence of free iron and intracellular redox potential. There are no known direct effects of nitric oxide on promoting caspase activation or activity. However, nitric oxide has been shown to promote apoptotic pathways in numerous cell types through the indirect activation of caspases. In this article we review the relationship of nitric oxide and caspase activity, modulation of this effect by iron, and clinical implications for the use of nitric oxide in regulating inflammation and apoptosis.
Kim
Peter K M
PK
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Kwon
Young-Guen
YG
Chung
Hun-Taeg
HT
Kim
Young-Myeong
YM
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*
D061945:Caspase Inhibitors; D007375:Interleukin-1; D020382:Interleukin-18; D009569:Nitric Oxide; D007501:Iron; D020169:Caspases