title: Generation of thiyl and ascorbyl radicals in the reaction of peroxynitrite with thiols and ascorbate at physiological pH.
abstract: Electron spin resonance (ESR) spin trapping was utilized to investigate the reaction of peroxynitrite with thiols and ascorbate at physiological pH. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The reaction of peroxynitrite with DMPO generated 5,5-dimethylpyrrolidone-(2)-oxy-(1) (DMPOX). Formate enhanced the peroxynitrite decomposition but did not generate any detectable amount of formate-derived free radicals. Thus, the spin trapping measurements provided no evidence for hydroxyl (.OH) radical generation in peroxynitrite decomposition at physiological pH. Thiols (glutathione, cysteine, and penicillamine) and ascorbate reacted with peroxynitrite to generate the corresponding thiyl and ascorbyl radicals. The one-electron oxidation of thiols by peroxynitrite may be one of the important mechanisms for peroxynitrite-induced toxicity and ascorbate may provide a detoxification pathway.
authors.affiliation: Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, Maryland 20892-0041.
authors.forename: X
authors.initials: X
authors.lastname: Shi
authors.forename: Y
authors.initials: Y
authors.lastname: Rojanasakul
authors.forename: P
authors.initials: P
authors.lastname: Gannett
authors.forename: K
authors.initials: K
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Mao
authors.forename: L N
authors.initials: LN
authors.lastname: Daniel
authors.forename: N
authors.initials: N
authors.lastname: Ahmed
authors.forename: U
authors.initials: U
authors.lastname: Saffiotti
mesh_terms: D001205:Ascorbic Acid / Q000737:chemistry*; D003497:Cyclic N-Oxides; D003683:Dehydroascorbic Acid / Q000031:analogs & derivatives*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D009566:Nitrates / Q000737:chemistry*; D013113:Spin Labels; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: C025634:5,5-dimethylpyrrolidin-2-one-1-oxide; D003497:Cyclic N-Oxides; D005609:Free Radicals; D009566:Nitrates; D013113:Spin Labels; D013438:Sulfhydryl Compounds; C039642:peroxynitric acid; C000820:semidehydroascorbic acid; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid