Alpha-tocopherol modulates human umbilical vein endothelial cell expression of Cu/Zn superoxide dismutase and catalase and lipid peroxidation.
Recent studies suggest the potential of alpha-tocopherol as a gene regulator, possibly through peroxisome proliferator-activated receptor gamma (PPARgamma) activation due to the structural similarity of alpha-tocopherol to a PPARgamma ligand, troglitazone. Other investigators have suggested that a link exists between induction of the antioxidant enzymes Cu/Zn superoxide dismutase (SOD) and catalase and PPARgamma activation. This study was designed to examine whether alpha-tocopherol modulates expression of Cu/Zn SOD and catalase in human umbilical vein endothelial cells through redox-sensitive transcription factors, PPARgamma, and nuclear factor-kappaB (NF-kappaB). Alpha-tocopherol treatments showed significant increases in both PPARgamma (1.4- to 2.2-fold, P < .01) and NF-kappaB p50 (1.3- to 1.5-fold, P < .005) DNA binding activities compared with vehicle control. Significant increases in Cu/Zn SOD mRNA levels (6.0-fold, P < .005) and catalase mRNA (8.0-fold, P < .005) and its protein levels (2.3-fold, P < .005) and lipid peroxidation levels (5.3-fold, P < .005) were observed at the lowest concentration (10 mumol/L) of alpha-tocopherol treatments. Both mRNA and protein levels of these 2 antioxidant enzymes were positively associated with lipid peroxidation (P < .05). Alpha-tocopherol may play a role not only in preventing against oxidative damage as an exogenous antioxidant by scavenging free radicals and superoxide but also in modulating the expression of the endogenous antioxidant enzymes as a gene regulator through PPARgamma and NF-kappaB in the vascular cells. The alpha-tocopherol-mediated gene expression is either stimulatory or inhibitory, depending on its oxidative status or its concentrations.
Nakamura
Yukiko K
YK
Department of Nutrition and Environmental Sciences and Health Graduate Program, University of Nevada, Reno, NV 89557, USA.
Omaye
Stanley T
ST
D002374:Catalase / Q000378:metabolism*; D002478:Cells, Cultured; D003300:Copper / Q000378:metabolism; D042783:Endothelial Cells / Q000201:enzymology*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D047495:PPAR gamma / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology; D015032:Zinc / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology*
D016328:NF-kappa B; D047495:PPAR gamma; D012333:RNA, Messenger; D003300:Copper; D002374:Catalase; D013482:Superoxide Dismutase; D024502:alpha-Tocopherol; D015032:Zinc