Peroxynitrite induces the conversion of xanthine dehydrogenase to oxidase in rabbit liver.
Effect of peroxynitrite (ONOO-) on the conversion of xanthine dehydrogenase to oxidase in rabbit liver was examined. ONOO- (25-200 microM) induced the conversion of xanthine dehydrogenase to oxidase in a dose-dependent manner. The addition of hydroxyl radical scavengers (mannitol and dimethyl sulfoxide) gave no alteration in the ONOO(-)-induced conversion of xanthine dehydrogenase to oxidase, implying that the action of ONOO- is not due to hydroxyl radicals which may be formed from ONOO-. The experiment utilizing dithiothreitol also revealed that the action of ONOO- might be due to oxidation of sulfhydryl group of xanthine dehydrogenase. These results suggest that ONOO- has the potential to convert xanthine dehydrogenase to oxidase, and that this effect may be correlated with cytotoxic actions of ONOO-.
Sakuma
S
S
Department of Hygienic Chemistry, Osaka University of Pharmaceutical Sciences, Nasahara, Takatsuki, Japan.
Fujimoto
Y
Y
Sakamoto
Y
Y
Uchiyama
T
T
Yoshioka
K
K
Nishida
H
H
Fujita
T
T
D000818:Animals; D003600:Cytosol / Q000201:enzymology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D017665:Hydroxyl Radical; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009566:Nitrates / Q000494:pharmacology*; D011817:Rabbits; D014968:Xanthine Dehydrogenase / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
D016166:Free Radical Scavengers; D009566:Nitrates; C039642:peroxynitric acid; D017665:Hydroxyl Radical; D008353:Mannitol; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D004229:Dithiothreitol; D004121:Dimethyl Sulfoxide