Tocopherol esters inhibit human glutathione S-transferase omega.
Human glutathione S-transferase omega 1-1 (hGSTO1-1) is a newly identified member of the glutathione S-transferase (GST) family of genes, which also contains alpha, mu, pi, sigma, theta, and zeta members. hGSTO1-1 catalyzes the reduction of arsenate, monomethylarsenate (MMA(V)), and dimethylarsenate (DMA(V)) and exhibits thioltransferase and dehydroascorbate reductase activities. Recent evidence has show that cytokine release inhibitory drugs, which specifically inhibit interleukin-1b (IL-1b), directly target hGSTO1-1. We found that (+)-alpha-tocopherol phosphate and (+)-alpha-tocopherol succinate inhibit hGSTO1-1 in a concentration-dependent manner with IC50 values of 2 microM and 4 microM, respectively. A Lineweaver-Burk plot demonstrated the uncompetitive nature of this inhibition. The molecular mechanism behind the inhibition of hGSTO1-1 by alpha-tocopherol esters (vitamin E) is important for understanding neurodegenerative diseases, which are also influenced by vitamin E.
Sampayo-Reyes
Adriana
A
División de Farmacología y Toxicología, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey Nuevo León, Mexico. adriana.sampayo@biomedicas.net
Zakharyan
Robert A
RA
D000975:Antioxidants / Q000494:pharmacology; D001152:Arsenicals / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D011994:Recombinant Proteins; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000031:analogs & derivatives* / Q000494:pharmacology
D000975:Antioxidants; D001152:Arsenicals; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D014810:Vitamin E; C012552:alpha-tocopherol phosphate; C490476:GSTO1 protein, human; D005982:Glutathione Transferase; D024502:alpha-Tocopherol; D024505:Tocopherols