Effect of vitamin E on human glutathione peroxidase (GSH-Px1) expression in cardiomyocytes

To determine the effect of vitamin E on cellular antioxidant enzymes, human ventricular cardiomyocytes were incubated with 200 mu M all-racemic-alpha-tocopheryl acetate for 14 d at pO(2)s of 150 and 30 mm Hg. Cellular Cu, Zn superoxide dismutase, catalase, and GSH-Px1 activities were measured. Although SOD and catalase activities were unaffected by a-tocopherol, GSH-Px1 activities increased (p < .0001) as much as twofold. This increase was independent of oxygen tension and selenium. The increase in GSH-Px1 activity became significant (p < .01) by day 4. A nonantioxidant analog of alpha-tocopherol, 200 mu M RRR-alpha-tocopherol methyl ether, did not affect GSH-Px1 activities. Although GSH-Px1 mRNA levels mirrored the changes in enzyme activities, the de novo nuclear GSHPx1 transcript synthesis was unaffected by alpha-tocopherol. Because the increase in GSH-Px1 activities also occurred after cellular alpha-tocopherol levels had plateaued, the above results were most consistent with posttranscriptional stabilization of GSH-Px1 mRNA by alpha-tocopherol or an alpha-tocopherol-related metabolic product.