Vitamin E: Regulatory Role on Signal Transduction

Abstract

Vitamin E modulates signal transduction pathways by several molecular mechanisms. As a hydrophobic molecule located mainly in membranes it contributes together with other lipids to the physical and structural characteristics such as membrane stability, curvature, fluidity, and the organization into microdomains (lipid rafts). By acting as the main lipid‐soluble antioxidant, it protects other lipids such as mono‐ and poly‐unsaturated fatty acids (MUFA and PUFA, respectively) against chemical reactions with reactive oxygen and nitrogen species (ROS and RNS, respectively) and prevents membrane destabilization and cellular dysfunction. In cells, vitamin E affects signaling in redox‐dependent and redox‐independent molecular mechanisms by influencing the activity of enzymes and receptors involved in modulating specific signal transduction and gene expression pathways. By protecting and preventing depletion of MUFA and PUFA it indirectly enables regulatory effects that are mediated by the numerous lipid mediators derived from these lipids. In recent years, some vitamin E metabolites have been observed to affect signal transduction and gene expression and their relevance for the regulatory function of vitamin E is beginning to be elucidated. In particular, the modulation of the CD36/FAT scavenger receptor/fatty acids transporter by vitamin E may influence many cellular signaling pathways relevant for lipid homeostasis, inflammation, survival/apoptosis, angiogenesis, tumorigenesis, neurodegeneration, and senescence. Thus, vitamin E has an important role in modulating signal transduction and gene expression pathways relevant for its uptake, distribution, metabolism, and molecular action that when impaired affect physiological and patho‐physiological cellular functions relevant for the prevention of a number of diseases. © 2018 IUBMB Life, 71(4):456–478, 2019

Vitamin E and cancer prevention: Studies with different forms of tocopherols and tocotrienols

“…Tocotrienols (α, β, γ, and δ‐T3) have the same substitution pattern of methyl groups on the chromanol ring as tocopherols, but they have an unsaturated 16‐carbon side chain with double bonds at the 3′‐, 7′‐, and 11′‐ positions (Figure 1). The hydrocarbon tail and ring structure provide the lipophilicity for VE molecules to be incorporated into the lipid bilayers of biological membranes or in lipoproteins 10 . The phenolic group in the chromanol moiety effectively quenches reactive free radicals by one electron reduction and prevents the propagation of free radical reactions in lipid peroxidation.…”

“…The hydrocarbon tail and ring structure provide the lipophilicity for VE molecules to be incorporated into the lipid bilayers of biological membranes or in lipoproteins. 10 The phenolic group in the chromanol moiety effectively quenches reactive free radicals by one electron reduction and prevents the propagation of free radical reactions in lipid peroxidation. The resulting tocopherol phenoxy radical can be reduced by ascorbic acid or glutathione to regenerate the tocopherol molecule.…”

“…In 2010, we reviewed the cancer‐preventive activities of tocopherols and tocotrienols 2 . Since then, this topic has been studied by a large number of investigators and reviewed by different authors 7–12 …”

“…2 Since then, this topic has been studied by a large number of investigators and reviewed by different authors. [7][8][9][10][11][12] A literature search on PubMed in June 2019 yielded 1804 articles on "vitamin E and cancer," 539 articles on "tocopherols and cancer," and 156 articles on "tocotrienols and cancer" for the past 10 years. The present article is an updated review of the cancerpreventive activities of different forms of VE in human and laboratory studies.…”

IUBMB‐Life 2019: Vitamin E—Regulatory Roles

“…As discussed in this issue (issue 71:4 ), many cellular regulatory effects of vitamin E and its metabolites have been recognized modulating apoptosis/cell survival, ferroptosis, cell proliferation, angiogenesis, lipid metabolism, membrane properties and repair, long term potentiation, signal transduction and gene expression. These cellular effects often go beyond a simple antioxidant action and most likely contribute to the beneficial regulatory effects of vitamin E observed in a number of diseases and conditions, ranging from atherosclerosis, inflammation, diabetes, obesity, infection, immune regulation, wound healing, ischemia/reperfusion injury, reproduction, age‐related macular degeneration (AMD), neurodegeneration, non‐alcoholic steatohepatitis (NASH), cancer/metastasis, senescence and aging.…”