Antioxidant mechanisms of nitric oxide against iron-catalyzed oxidative stress in cells.
Three distinct antioxidant pathways are considered through which iron-catalyzed oxidative stress may be regulated by nitric oxide (NO). The first two pathways involve direct redox interactions of NO with iron catalytic sites and represent a fast response that may be considered an emergency mechanism to protect cells from the consequences of acute and intensive oxidative stress. These are (i) NO-induced nitrosylation at heme and non-heme iron catalytic sites that is capable of directly reducing oxoferryl-associated radicals, (ii) formation of nitrosyl complexes with intracellular "loosely" bound redox-active iron, and (iii) an indirect regulatory pathway that may function as an adaptive mechanism that becomes operational upon long-term exposure of cells to NO. In the latter pathway, NO down-regulates expression of iron-containing proteins to prevent their catalytic prooxidant reactions.
Kagan
V E
VE
Department of Environmental and Occupational Health, University of Pittsburgh, PA 15238, USA. kagan@pitt.edu
Kozlov
A V
AV
Tyurina
Y Y
YY
Shvedova
A A
AA
Yalowich
J C
JC
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D016166:Free Radical Scavengers / Q000378:metabolism*; D006420:Hemeproteins / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry; D006801:Humans; D007501:Iron / Q000494:pharmacology*; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D016601:RNA-Binding Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000378:metabolism
D000975:Antioxidants; D016166:Free Radical Scavengers; D006420:Hemeproteins; D006454:Hemoglobins; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D020122:tert-Butylhydroperoxide; D007501:Iron