Retinoids inhibit mammalian glutathione transferases.
Affinity-purified cytosolic glutathione transferases from adult female rat liver, adult human liver and human term placenta were used. Of the 8 retinoids tested, all-trans retinoic acid was found to be the most potent inhibitor of placental glutathione transferase. The inhibition was non-competitive and exhibited Ki values of 20 and 41 microM for all-trans retinoic acid in the presence of varying concentrations of 1-chloro-2,4-dinitrobenzene and glutathione, respectively. Micromolar all-trans retinoic acid also caused significant (30-90%) inhibition of rat and human liver glutathione transferases. Taken together, the data suggest that inhibition of glutathione transferase(s) may represent yet another mechanism of retinoid action.
Kulkarni
A A
AA
Florida Toxicology Research Center, Department of Environmental and Occupational Health, College of Public Health, University of South Florida, Tampa 33612-3805, USA.
Kulkarni
A P
AP
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D005260:Female; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D006801:Humans; D010920:Placenta / Q000201:enzymology; D051381:Rats; D012176:Retinoids / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014212:Tretinoin / Q000494:pharmacology
D000970:Antineoplastic Agents; D012176:Retinoids; D014212:Tretinoin; D005982:Glutathione Transferase