Nitric oxide prevents oxidative damage produced by tert-butyl hydroperoxide in erythroleukemia cells via nitrosylation of heme and non-heme iron. Electron paramagnetic resonance evidence.

Abstract	We studied protective effects of NO against tert-butylhydroperoxide (t-BuOOH)-induced oxidations in a subline of human erythroleukemia K562 cells with different intracellular hemoglobin (Hb) concentrations. t-BuOOH-induced formation of oxoferryl-Hb-derived free radical species in cells was demonstrated by low temperature EPR spectroscopy. Intensity of the signals was proportional to Hb concentrations and was correlated with cell viability. Peroxidation of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and cardiolipin metabolically labeled with oxidation-sensitive cis-parinaric acid was induced by t-BuOOH. An NO donor, (Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]-diazen-1-iu m-1, 2-diolate], produced non-heme iron dinitrosyl complexes and hexa- and pentacoordinated Hb-nitrosyl complexes in the cells. Nitrosylation of non-heme iron centers and Hb-heme protected against t-BuOOH-induced: (a) formation of oxoferryl-Hb-derived free radical species, (b) peroxidation of cis-parinaric acid-labeled phospholipids, and (c) cytotoxicity. Since NO did not inhibit peroxidation induced by an azo-initiator of peroxyl radicals, 2, 2'-azobis(2,4-dimethylvaleronitrile), protective effects of NO were due to formation of iron-nitrosyl complexes whose redox interactions with t-BuOOH prevented generation of oxoferryl-Hb-derived free radical species.
Authors	N V Gorbunov, J C Yalowich, A Gaddam, P Thampatty, V B Ritov, E R Kisin, N M Elsayed, V E Kagan
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 272 Issue 19 Pg. 12328-41 (May 09 1997) ISSN: 0021-9258 [Print] United States
PMID	9139677 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Free Radicals Hemoglobins Peroxides Reactive Oxygen Species Nitric Oxide Heme tert-Butylhydroperoxide
Topics	Cell Survival Electron Spin Resonance Spectroscopy Free Radicals Heme (metabolism) Hemoglobins (metabolism) Humans Kinetics Leukemia, Erythroblastic, Acute (metabolism) Nitric Oxide (pharmacology) Oxidative Stress Peroxides (pharmacology) Reactive Oxygen Species (metabolism) Tumor Cells, Cultured tert-Butylhydroperoxide

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