Antioxidant mechanisms of nitric oxide against iron-catalyzed oxidative stress in cells.
Kagan-VE; Kozlov-AV; Tyurina-YY; Shvedova-AA; Yalowich-JC
Antioxid Redox Signal 2001 Apr; 3(2):189-202
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.
Antioxidants; Oxides; Stress; Proteins; Reaction-rates; Oxidative-processes; Iron-oxides; Exposure-levels
Dr. Valerian E. Kagan, Department of Environmental and Occupational Health, University of Pittsburgh, 260 Kappa Dr., RIDC Park, Pittsburgh, PA 15238, U.S.A.
Antioxidants & Redox Signaling