Inhibition of human glutathione S-transferase P1-1 by tocopherols and α-tocopherol derivatives

摘要

α-Tocopherol inhibits glutathione S-transferase P1-1 (GST P1-1) (R.I.M. van Haaften, C.T.A. Evelo, G.R.M.M. Haenen, A. Bast, Biochem. Biophys. Res, Commun. 280 (2001)). In various cosmetic and dietary products α-tocopherol is added as a tocopherol ester. Therefore we have studied the effect of various tocopherol derivatives on GST P1-1 activity. It was found that GST P1-1 is inhibited, in a concentration dependent manner, by these compounds. Of the compounds tested, the tocopherols were the most potent inhibitors of GST P1-1; the concentration giving 50% inhibition (IC_(50)) is ＜ 1 μM. The esterified tocopherols and α-tocopherol quinone also inhibit the GST P1-1 activity at a very low concentration: for most compounds the IC_(50) was below 10 μM. RRR-α-Tocopherol acetate lowered the V_(max) values, but did not affect the K_m for either 1-chloro-2,4-dinitrobenzene or GSH. This indicates that the GST P1-1 enzyme is non-competitively inhibited by RRR-α-tocopherol acetate. The potential implications of GST P1-1 inhibition by tocopherol and α-tocopherol derivatives are discussed.