title: Thioredoxin-dependent sulfoxide reduction by rat renal cytosol.
abstract: The reduction of sulindac to sulindac sulfide by rat renal enzymes has been characterized. This biotransformation is catalyzed by cytosolic enzymes requiring NADPH. The KM and Vmax for sulindac were 45.0 +/- 13.1 microM and 0.48 +/- 0.15 nmol of sulindac sulfide per 5 mg of protein per min, respectively. The reaction was inhibited by sulfhydryl reagents and several sulfoxides. Furthermore, disulfides [insulin, glutathione disulfide, L-cystine, and 5,5'-dithiobis (2-nitrobenzoic acid)] known to interact with thioredoxin-dependent enzyme systems inhibited sulindac reduction, as did sodium arsenite, a known inhibitor of thioredoxin reductase. Removal of thioredoxin from renal cytosolic fractions by gel-filtration chromatography resulted in a marked diminution of sulindac reduction: activity was restored by addition of purified Escherichia coli thioredoxin or dithiothreitol. These findings demonstrate the involvement of thioredoxin in renal sulfoxide reduction.
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D003553:Cystine / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D007192:Indenes / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D013454:Sulfoxides / Q000378:metabolism*; D013467:Sulindac / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D007192:Indenes; D007328:Insulin; D013454:Sulfoxides; D013467:Sulindac; D003553:Cystine; D013879:Thioredoxins; D004228:Dithionitrobenzoic Acid; D005978:Glutathione