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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin E is one of the most abundant lipid-soluble antioxidant agents found in plasma and cells of higher mammals. The uptake, transport and tissue delivery of alpha-tocopherol, a key vitamin E form, involves molecular, biochemical, and cellular processes closely related to overall lipid and lipoprotein homeostasis. This review highlights recent findings that have led to a better understanding of vitamin E transport, including intestinal absorption, hepatic transport, and cellular uptake of alpha-tocopherol in vivo. This new information may be critical for manipulation of vitamin E homeostasis in a variety of oxidative stress-related disease conditions in humans.
Mol Aspects Med
PMID:Absorption, transport, and tissue delivery of vitamin E. 1732 Jan 65

Efflux pump (e.g., P-gp, MRP1, and BCRP) inhibition has been recognized as a strategy to overcome multi-drug resistance and improve drug bioavailability. Besides small-molecule inhibitors, surfactants such as Tween 80, Cremophor EL, several Pluronics, and Vitamin E TPGS (TPGS 1000) are known to modulate efflux pump activity. Competitive inhibition of substrate binding, alteration of membrane fluidity, and inhibition of efflux pump ATPase have been proposed as possible mechanisms. Focusing on TPGS 1000, the aim of our study was to unravel the inhibitory mechanism by comparing the results of inhibition experiments in a Caco-2 transport assay with data from electron spin resonance (ESR) and from ATPase activity studies. ESR results, on Caco-2 cells using 5-doxyl stearic acid (5-SA) as a spin probe, ruled out cell membrane fluidization as a major contributor; change of membrane fluidity was only observed at surfactant concentrations 100 times higher than those needed to achieve full efflux inhibition. Concurrently, TPGS 1000 inhibited substrate induced ATPase activity without inducing significant ATPase activity on its own. By investigating TPGS analogues that varied by their PEG chain length, and/or possessed a modified hydrophobic core, transport studies revealed that modulation of ATPase activity correlated with inhibitory potential for P-gp mediated efflux. Hence, these results indicate that ATPase inhibition is an essential factor in the inhibitory mechanism of TPGS 1000 on cellular efflux pumps.
Mol Pharm
PMID:Mechanism of inhibition of P-glycoprotein mediated efflux by vitamin E TPGS: influence on ATPase activity and membrane fluidity. 1736 62

The protective effect of vitamins E (alpha-tocopherol) and C (L-ascorbic acid) in the prevention of cardiovascular disease (CVD) has been shown in a number of situations but a secure correlation is not universally accepted. Under certain conditions, both, L-ascorbic acid and alpha-tocopherol can exhibit antioxidant properties and thus may reduce the formation of oxidized small molecules, proteins and lipids, which are a possible cause of cellular de-regulation. However, non-antioxidant effects have also been suggested to play a role in the prevention of atherosclerosis. Vitamin E and C can modulate signal transduction and gene expression and thus affect many cellular reactions such as the proliferation of smooth muscle cells, the expression of cell adhesion and extracellular matrix molecules, the production of O(2)(-) by NADPH-oxidase, the aggregation of platelets and the inflammatory response. Vitamins E and C may modulate the extracellular matrix environment by affecting VSMC differentiation and the expression of connective tissue proteins involved in vascular remodeling as well as the maintenance of vascular wall integrity. This review summarizes individually the molecular activities of vitamins E and C on the cells within the connective tissue of the vasculature, which are centrally involved in the maintenance of an intact vascular wall as well as in the repair of atherosclerotic lesions during disease development.
Mol Aspects Med
PMID:Regulatory role of vitamins E and C on extracellular matrix components of the vascular system. 1762 19

Vitamin E has been used for more than 50 years in experimental and clinical dermatology. While a large number of case reports were published in this time, there is still a lack of controlled clinical studies providing a rationale for well defined dosages and clinical indications. In contrast, advances in basic research on the physiology, mechanism of action, penetration, bioconversion and photoprotection of vitamin E in human skin has led to the development of numerous new formulations for use in cosmetics and skin care products. This article reviews basic mechanisms and possible cosmetic as well as clinical implications of the recent advances in cutaneous vitamin E research. Experimental evidence suggests that topical and oral vitamin E has antitumorigenic, photoprotective, and skin barrier stabilizing properties. While the current use of vitamin E is largely limited to cosmetics, controlled clinical studies for indications such as atopic dermatitis or preventions of photocarcinogenesis are needed to evaluate the clinical benefit of vitamin E.
Mol Aspects Med
PMID:Vitamin E in human skin: organ-specific physiology and considerations for its use in dermatology. 1771 81

Randomised clinical trials and epidemiologic studies addressing the preventive effects of vitamin E supplementation against cardiovascular disease reported both positive and negative effects, and recent meta-analyses of the clinical studies were rather disappointing. In contrast to that, many animal studies clearly show a preventive action of vitamin E in several experimental settings, which can be explained by the molecular and cellular effects of vitamin E observed in cell cultures. This review is focusing on the molecular effects of vitamin E on the cells playing a role during atherosclerosis, in particular on the endothelial cells, vascular smooth muscle cells, monocytes/macrophages, T cells, and mast cells. Vitamin E may act by normalizing aberrant signal transduction and gene expression in antioxidant and non-antioxidant manners; in particular, over-expression of scavenger receptors and consequent foam cell formation can be prevented by vitamin E. In addition to that, the cellular effects of alpha-tocopheryl phosphate and of EPC-K1, a composite molecule between alpha-tocopheryl phosphate and l-ascorbic acid, are summarized.
Mol Aspects Med
PMID:Cellular, molecular and clinical aspects of vitamin E on atherosclerosis prevention. 1782 3

The goal of these studies was to investigate the potential anticancer properties of two naturally occurring plant sources and two manufactured synthetic forms of vitamin E, i. e., RRR-alpha-tocopherol (alphaT), RRR-gamma-tocopherol (gammaT), all-rac-alpha-tocopherol (all-rac-alphaT), and all-rac-alpha-tocopheryl acetate (all-rac-alphaTAc) in breast cancer models. Vitamin E compounds were evaluated in vitro for inhibition of colony formation and induction of apoptosis in human MDA-MB-435 and MCF-7 breast cancer cells and murine 66cl-4 mammary cancer cells and in vivo for ability to reduce tumor growth and lung and lymph node metastases using the transplantable syngeneic BALB/c mouse 66cl-4-GFP mammary cancer model. gammaT inhibited colony formation and induced apoptosis in all three cancer cell lines. alphaT and all-rac-alphaT were less effective and all-rac-alphaTAc was ineffective. gammaT-induced apoptosis was correlated with activation of caspases-8 and -9 and down-regulation of protein expression of c-FLIP and survivin. In vivo study 1 analyses showed that all-rac-alphaT and all-rac-alphaTAc significantly inhibited tumor growth and inhibited both visible and microscopic size lung metastases. In vivo study 2 analyses showed that alphaT and gammaT reduced tumor growth, but only gammaT reduced tumor growth significantly in comparison to control. In conclusion, synthetic, but not natural, vitamin E exhibits promising anti-cancer properties in vivo.
Mol Nutr Food Res 2008 Apr
PMID:In vitro and in vivo evaluation of anticancer actions of natural and synthetic vitamin E forms. 1838 78

NAG-1 (nonsteroidal anti-inflammatory drug-activated gene), a member of the transforming growth factor-beta superfamily, is involved in many cellular processes, such as inflammation, apoptosis/survival, and tumorigenesis. Vitamin E succinate (VES) is the succinate derivative of alpha-tocopherol and has antitumorigenic activity in a variety of cell culture and animal models. In the current study, the regulation and role of NAG-1 expression in PC-3 human prostate carcinoma cells by VES was examined. VES treatment induced growth arrest and apoptosis as well as an increase in NAG-1 protein and mRNA levels in a time- and concentration-dependent manner. VES treatment induced nuclear translocation and activation of p38 kinase. Pretreatment with p38 kinase inhibitor blocked the VES-induced increase in NAG-1 protein and mRNA levels, whereas an inhibition of protein kinase C, Akt, c-Jun NH(2)-terminal kinase, or MEK activity had no effect on VES-induced NAG-1 levels. Forced expression of constitutively active MKK6, an upstream kinase for p38, induced an increase in NAG-1 promoter activity, whereas p38 kinase inhibitor blocked MKK6-induced increase in NAG-1 promoter activity. VES treatment resulted in >3-fold increase in the half-life of NAG-1 mRNA in a p38 kinase-dependent manner and transient transfection experiment showed that VES stabilizes NAG-1 mRNA through AU-rich elements in 3'-untranslated region of NAG-1 mRNA. The inhibition of NAG-1 expression by small interfering RNA significantly blocked VES-induced poly(ADP-ribose) polymerase cleavage, suggesting that NAG-1 may play an important role in VES-induced apoptosis. These results indicate that VES-induced expression of NAG-1 mRNA/protein is regulated by transcriptional/post-transcriptional mechanism in a p38 kinase-dependent manner and NAG-1 can be chemopreventive/therapeutic target in prostate cancer.
Mol Cancer Ther 2008 Apr
PMID:Vitamin E succinate induces NAG-1 expression in a p38 kinase-dependent mechanism. 1841 10

Prostate and colorectal cancers are among the most common cancers and identifying modifiable risk factors are important steps to reduce the burden of these severe diseases. Results from several but mostly small observational studies as well as the secondary analysis of an intervention trial provide support for a chemopreventive effect of selenium on prostate and colorectal cancers. Results suggest effect modification by gender and smoking, but this interpretation is limited by the statistical power of previous studies. Several cancer preventive mechanisms have been described and it is likely that selenium acts through multiple pathways. In particular, the anti-oxidative and anti-inflammatory effects mediated through activity of selenoenzymes are discussed, given the relevance of oxidative stress and inflammation in these cancers. Genetic variation in selenoenzymes may modify the potential chemopreventive effect of selenium and need to be further investigated. Additional large observational studies using biomarkers of selenium intake and intervention trials, such as the Selenium and Vitamin E Cancer Prevention Trial, will be important to further evaluate the potential chemopreventive effect of selenium. Furthermore, characterization of functional effects of polymorphisms in selenoenzymes is needed.
Mol Nutr Food Res 2008 Nov
PMID:Selenium and the prevention of prostate and colorectal cancer. 1876 56

This study was conducted to test whether oxidative stress activates the intracellular protein kinase B (AKT1) signaling pathway, which culminates with cardiac hypertrophy in experimental hyperthyroidism. Male Wistar rats were divided into four groups: control, vitamin E, thyroxine (T(4)), and T(4)+vitamin E. Hyperthyroidism was induced by T(4) administration (12 mg/l in drinking water for 28 days). Vitamin E treatment was given during the same period via s.c. injections (20 mg/kg per day). Morphometric and hemodynamic parameters were evaluated at the end of the 4-week treatment period. Protein oxidation, redox state (reduced glutathione, GSH/glutathione dissulfide, GSSG), vitamin C, total radical-trapping antioxidant potential (TRAP), hydrogen peroxide (H2O2), and nitric oxide metabolites (NO(X)) were measured in heart homogenates. The p-AKT1/AKT1 ratio, p-glycogen-synthase kinase (GSK)3B/GSK3B ratio, FOS, and JUN myocardial protein expression were also quantified by western blot after 4 weeks. Increases in biochemical parameters, such as protein oxidation (41%), H2O2 (62%), and NO(X) (218%), and increase in the left ventricular end-diastolic pressure were observed in the T(4) group. T(4) treatment also caused a decrease in GSH/GSSG ratio (83%), vitamin C (34%), and TRAP (55%). These alterations were attenuated by vitamin E administration to the hyperthyroid rats. Expression of p-AKT1/AKT1, p-GSK3B/GSK3B, FOS, and JUN were elevated in the T(4) group (by 69, 37, 130, and 33% respectively), whereas vitamin E administration promoted a significant reduction in their expression. These results indicate that oxidative stress plays an important role in cardiac hypertrophy, and suggest redox activation of AKT1 and JUN/FOS signaling pathways with H2O2 acting as a possible intracellular mediator in this adaptive response to experimental hyperthyroidism.
J Mol Endocrinol 2008 Dec
PMID:The role of redox signaling in cardiac hypertrophy induced by experimental hyperthyroidism. 1878 53

Information about lipid oxidation in fresh and stored human milk compared with infant formulas is scarce. We aimed to assess n-6 and n-3 PUFA oxidation in these milks by measuring the 4-hydroxynonenal (4-HNE) and 4-hydroxyhexenal (4-HHE) content. Human milk samples (n = 4), obtained from volunteer mothers, were analyzed fresh and after 1 wk at 4 degrees C or 24 h at 18 degrees C. Vitamin E and malondialdehyde (MDA) were measured by HPLC and fatty acid profile by GC. The 4-HHE and 4-HNE contents were measured by GC-MS. Infant formulas (n = 10) were tested; their fat droplet size was measured by laser light scattering and observed by confocal laser scanning microscopy. Human milk samples contained 31.0 +/- 6.3 g/L of lipids and 1.14 +/- 0.26 mg/L of vitamin E. Fat droplets were smaller in infant formulas than reported in human milk. The (4-HHE/n-3 PUFA) ratio was 0.19 +/- 0.01 microg/g in fresh human milk (unchanged after storage) versus 3.6 +/- 3.1 microg/g in dissolved powder formulas and 4.3 +/- 3.8 microg/g in liquid formula. (4-HNE/n-6 PUFA) was 0.004 +/- 0.000 microg/g in fresh milk (0.03 +/- 0.01 microg/g after storage) versus 1.1 +/- 1.0 microg/g in dissolved powder formulas and 0.2 +/- 0.3 microg/g in liquid formula. Infant formulas also contained more MDA than human milk. n-3 PUFA were more prone to oxidation than n-6 PUFA. Whether threshold levels of 4-HHE and 4-HNE would be of health concern should be elucidated.
Mol Nutr Food Res 2008 Dec
PMID:Oxidation products of polyunsaturated fatty acids in infant formulas compared to human milk--a preliminary study. 1879 26


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