Antioxidant Independent Actions of Vitamin E in Modulating Gene Expression

Alpha-tocopherol (vitamin E) is a plant-derived lipid antioxidant that is an essential nutrient for all vertebrates. The vitamin’s function in reducing and preventing injury caused by reactive oxygen species (ROS) has been well established. Recently, a few lines of evidence indicated that alpha tocopherol has novel functions in addition to its established radical-quenching activity, specifically in regulating gene expression. To investigate this issue, we asked whether an analog of vitamin E that has no antioxidant activity, 6-hydroxymethyl alpha tocopherol (6HMTC), is able to regulate expression of the TTPAgene, encoding the tocopherol transfer protein, TTP, an activity exhibited by the natural vitamin. We found that the analog 6HMTC is not an effective antioxidant in vitro and in cultured hepatocytes. However, 6HMTC induced expression of the TTPA gene in cells in a manner indistinguishable from alpha-tocopherol. These results indicate that the biological actions of vitamin E involve yet-unexplored, antioxidant-independent mechanisms. Future work will be directed into the molecular pathways that mediate this phenomenon, and the roles it plays in specific health-promoting effects of vitamin E.