Nakamura Yukiko K, Omaye Stanley T
Department of Nutrition and Environmental Sciences and Health Graduate Program, University of Nevada, Reno, NV 89557, USA.
Nutr Res. 2008 Oct;28(10):671-80. doi: 10.1016/j.nutres.2008.07.002.
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.
最近的研究表明，α-生育酚可能具有作为基因调节剂的潜力，这可能是由于α-生育酚与过氧化物酶体增殖物激活受体γ（PPARγ）配体曲格列酮在结构上相似，从而激活了PPARγ。其他研究人员指出，抗氧化酶铜/锌超氧化物歧化酶（SOD）和过氧化氢酶的诱导与PPARγ激活之间存在联系。本研究旨在探讨α-生育酚是否通过氧化还原敏感转录因子、PPARγ和核因子-κB（NF-κB）调节人脐静脉内皮细胞中铜/锌SOD和过氧化氢酶的表达。与载体对照相比，α-生育酚处理显示PPARγ（1.4至2.2倍，P <.01）和NF-κB p50（1.3至1.5倍，P <.005）的DNA结合活性均显著增加。在α-生育酚处理的最低浓度（10μmol/L）下，观察到铜/锌SOD mRNA水平（6.0倍，P <.005）、过氧化氢酶mRNA（8.0倍，P <.005）及其蛋白水平（2.3倍，P <.005）和脂质过氧化水平（5.3倍，P <.005）显著增加。这两种抗氧化酶的mRNA和蛋白水平均与脂质过氧化呈正相关（P <.05）。α-生育酚不仅可能作为一种外源性抗氧化剂通过清除自由基和超氧化物来预防氧化损伤，还可能作为一种基因调节剂通过PPARγ和NF-κB调节血管细胞中内源性抗氧化酶的表达。α-生育酚介导的基因表达取决于其氧化状态或浓度，可能具有刺激或抑制作用。
