Tocopherols, modulating activity

Vitamin E (tocopherol), which is a major lipid-soluble antioxidant, inhibits the differentiation of smooth muscle presumably by modulating the activity of protein kinase C. PKC inhibition by tocopherol has also been implied in human platelets. 

Stauble, B., Boscoboinik, D., Tasinato, A., and Azzi, A. (1994). Modulation of activator protein-1 (AP-1) transcription factor and protein kinase C by hydrogen peroxide and D-alpha-tocopherol in vascular smooth muscle cells. Eur J Biochem 226, 393-402. 

Protein kinase C (PKC) is a family of enzymes that plays a major role in cell signaling and the modulation of gene expression related to cell growth, proliferation, and differentiation. PKC activation may also play a critical role in tumor promotion in some types of cancer. a-Tocopherol has been found to inhibit PKCa activity in a number of cell types and in animal models of atherosclerosis. PKCa inhibition by a-tocopherol appears umelated to its antioxidant function rather, oc-tocopherol may inhibit PKCa activity by promoting its dephosphorylation or by modulating diacylglycerol kirrase activity. ... 

The tocopherols may be metabolized to bioactive compounds, such as Simon metabolites, CEHCs, or tocopheryl quinones (see sections on tocopherol metabolites and tocopheryl quinones), which can bind to transcription factors and enzymes and modulate their activity. 

In addition to antioxidant activity, there are specific a-tocopherol-dependent functions that normalize cellular functions in a variety of cells. a-Tocopherol plays a critical role through its ability to inhibit the activity of protein kinase C, a central player in many signal transduction pathways. Specifically, it modulates pathways of platelet aggregation, endothelial cell nitric oxide production, monocyte/macrophage superoxide production, and smooth muscle cell proliferation. Regulation of adhesion molecule expression and inflammatory cell cytokine production by a-tocopherol has also been reported. However, most of the information in this area has been obtained from in vitro studies. More studies in hiunans are needed to relate a-tocopherol intakes and tissue concentrations to optimal tissue responses. 

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