Vitamin E: A Role in Signal Transduction

Abstract

Vitamin E modulates the activity of several signal transduction enzymes with consequent alterations of gene expression. At the molecular level, vitamin E may directly bind to these enzymes and compete with their substrates, or it may change their activity by redox regulation. The translocation of several of these enzymes to the plasma membrane is regulated by vitamin E, suggesting the modulation of protein-membrane interactions as a common mechanism for vitamin E action. Enzyme-membrane interactions can be affected by vitamin E by interference with binding to specific membrane lipids or by altering cellular structures such as membrane microdomains (lipid rafts). Moreover, competition by vitamin E for common binding sites within lipid transport proteins may alter the traffic of lipid mediators and thus affect their signaling and enzymatic conversion. In this review, the main effects of vitamin E on enzymes involved in signal transduction are summarized and possible molecular mechanisms leading to enzyme modulation are evaluated.

Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells

“…These data support the hypothesis that the protective effect of α-tocopherol does not depend on the cell type considered, whereas the protective effect of γ-tocopherol is cell-type specific. As Trolox, which is a strong antioxidant, provided no protection against the toxic effects of 7KC, our data suggest that the anti-oxidative properties of α- and γ-tocopherol are not essential to prevent these toxic effects of 7KC, and that the protective activities of these tocopherols involve other mechanisms [38,39,40,77]. Our observations are in agreement with data reporting that all of the stereoisomers and derivatives of Vitamin E have antioxidant activities and that small differences exist for each form [38,39,78].…”

“…This demonstrates that molecules able to prevent the toxic effects of 7KC can be active by involving mechanisms other than those associated with their antioxidant power. With tocopherols, several mechanisms are also probably involved: (i) impairment of 7KC accumulation in lipid rafts [34,41]; (ii) changes in the surface exposure of membrane receptors; and (iii) modulation of signal transduction by modifying plasma membrane properties [77,86]. Moreover, as it has been reported that the cytoprotective properties of α-tocopherol are mostly related to gene regulation rather than to antioxidant activity in toxin-induced cell death in hepatocytes [87], similar mechanisms cannot be excluded in the ability of tocopherols to prevent the toxic effects of 7KC.…”

Bioavailability of Vitamin E

“…It acts as a chain-breaking antioxidant, especially against peroxyl radicals, and is thus essential in maintaining the integrity of long-chain polyunsaturated fatty acids found in cell membranes (9). Recently, it has been shown to also exert non-antioxidant activities (10): modulation of gene expression (11,12), inhibition of cell proliferation (13), regulation of bone mass (14)… Since oxidative stress has been implicated in the aetiology of several diseases, e.g. cardiovascular diseases and cancers, numerous epidemiological studies have investigated the association between VE dietary intake or status (usually evaluated as the fasting blood -tocopherol concentration) and the incidence of these diseases and reported negative associations (15)(16)(17).…”

Antioxidants as therapeutics in the intensive care unit: Have we ticked the redox boxes?

“…For instance, vitamin C, beyond its celebrated antioxidant activity, has been implicated as cofactor in several metabolic pathways, such as the synthesis of noradrenaline and carnitine, the post-translational modification of collagen, the catabolism of tyrosine, the calcium management in bones and a wide spectrum of immune-related processes [45,46,47,48]. Likewise, vitamin E exerts many non-antioxidants activities (predominately the α-tocopherol isoform) including modulation of gene expression, inhibition of smooth muscle cell proliferation, preservation of endothelial integrity as well as inhibition of platelet and monocyte-endothelial adhesion [49,50,51,52,53]. On this basis, a challenging question is whether the outcomes of a combined "antioxidant" intervention with vitamins C and E are mediated by their redox or non-redox properties.…”