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-.