Nitric oxide inhibits peroxynitrite-induced production of hydroxyeicosatetraenoic acids and F2-isoprostanes in phosphatidylcholine liposomes.
Lipid peroxidation is a component of various pathologies associated with nitric oxide (NO). It has been suggested that in vivo production of peroxynitrite (ONOO-) is responsible for the detrimental effects of pathologies associated with NO. To investigate the role of NO and ONOO- in the formation of specific lipid peroxidation products, liposomes of phosphatidylcholine were incubated at 37 degrees C for 1 h with various NO sources [NO, diethylamine NONOate (DEA/NO)] or ONOO-sources [3-morpholinosydnonimine-HCl (Sin-1), ONOO-]. Gas chromatography-mass spectrometry was used to quantify the formation of hydroperoxy- and hydroxyeicosatetraenoic acids (HETEs) and F2-isoprostanes. Peroxynitrite (0.5 mm) caused significant oxidation of phosphatidylcholine liposomes as measured by the increased formation of HETEs and F2-isoprostanes. NO, either added directly to the liposomes as a bolus or delivered by slow diffusion or via the donor compound DEA/NO, caused no lipid peroxidation itself and significantly inhibited both iron- and ONOO--induced lipid peroxidation. Sin-l (1 mM), which releases both NO and superoxide, resulted in minor increases in peroxidation and did not inhibit iron-induced HETE formation. We conclude that peroxynitrite but not nitric oxide can directly cause lipid peroxidation and that NO can act as an antioxidant by terminating lipid radical chain propagation reactions.
Laskey
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Biochemistry, The Upjohn Company, Kalmazoo, Michigan 49001, USA.
Mathews
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D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D002417:Cattle; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis / Q000737:chemistry*; D015227:Lipid Peroxidation; D008081:Liposomes; D008099:Liver; D009566:Nitrates; D009569:Nitric Oxide; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines
D006893:Hydroxyeicosatetraenoic Acids; D008081:Liposomes; D009566:Nitrates; D010713:Phosphatidylcholines; C039642:peroxynitric acid; D009569:Nitric Oxide; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C027356:11-hydroxy-5,8,12,14-eicosatetraenoic acid; C047628:8-hydroxyeicosatetraenoic acid; D015237:Dinoprost