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 microM all-racemic-alpha-tocopheryl acetate for 14 d at pO2s of 150 and 40 mm Hg. Cellular Cu, Zn superoxide dismutase, catalase, and GSH-Px1 activities were measured. Although SOD and catalase activities were unaffected by alpha-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 microM 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 GSH-Px1 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.
Li
R K
RK
Department of Clinical Biochemistry, Toronto Hospital, Ontario, Canada.
Cowan
D B
DB
Mickle
D A
DA
Weisel
R D
RD
Burton
G W
GW
D000704:Analysis of Variance; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003470:Culture Media; D005979:Glutathione Peroxidase / Q000096:biosynthesis* / Q000378:metabolism; D006352:Heart Ventricles; D006801:Humans; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology*; D010100:Oxygen / Q000032:analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D012643:Selenium / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D024505:Tocopherols; D014158:Transcription, Genetic / Q000187:drug effects*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000031:analogs & derivatives*
D000975:Antioxidants; D003470:Culture Media; D012333:RNA, Messenger; D014810:Vitamin E; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D024502:alpha-Tocopherol; D012643:Selenium; D024505:Tocopherols; D010100:Oxygen