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 th e 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 K-i values of 20 and 41 mu M for al l-trans retinoic acid in the presence of varying concentrations of 1-c hloro-2,4-dinitrobenzene and glutathione, respectively. Micromolar all -trans retinoic acid also caused significant (30-90%) inhibition of ra t and human liver glutathione transferases. Taken together, the data s uggest that inhibition of glutathione transferase(s) may represent yet another mechanism of retinoid action.