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Vitamins and Hormones 2007Vitamin E comprises a group of compounds possessing vitamin E activity. alpha-Tocopherol is the compound demonstrating the highest vitamin E activity, which is available... (Review)
Review
Vitamin E comprises a group of compounds possessing vitamin E activity. alpha-Tocopherol is the compound demonstrating the highest vitamin E activity, which is available both in its natural form as RRR-alpha-tocopherol isolated from plant sources, but more common as synthetically manufactured all-rac-alpha-tocopherol. Synthetic all-rac-alpha-tocopherol consists of a racemic mixture of all eight possible stereoisomers. Assessing the correct biological activity in form of bioavailability and biopotency has been a great challenge during many years as it is difficult to measure clinical endpoints in larger animals than rats and poultry. Thus, the biological effects in focus are resorption of fetuses, testicular degeneration, muscle dystrophy, anemia, encephalomalacia, and in recent years the influence of vitamin E on the immune system are the most important clinical markers of interest. For humans and animals, only different biomarkers or surrogate markers of bioactivity have been measured. In studies with rats, a good consistency between the classical resorption-gestation test and the bioavailability of the individual stereoisomers in fluids and tissues has been shown. For humans and other animals, only different biomarkers or surrogate markers of bioactivity have been measured, and due to the lack of good biological markers for bioactivities, bioavailability is often used as one of the surrogate markers for bioactivities with those limitations this must give. Therefore, a relatively simple analytical method, which allows analysis of the individual stereoisomers of alpha-tocopherol, is an important tool in order to quantify relative bioavailability of the individual stereoisomers. The analytical method presented here allows the quantification of total tocopherol content and composition by normal phase HPLC and subsequent separation of the stereoisomers of alpha-tocopherol as methyl ethers by chiral HPLC. Using this method, the alpha-tocopherol stereoisomers are separated into five peaks. The first peak consists of the four 2S isomers (SSS-, SSR-, SRR-, SRS-), the second peak consists of RSS-, the third peak consists of RRS-, the fourth peak consists of RRR-, and the fifth peak consists of RSR-alpha-tocopherol. The discussion on the bioavailability of RRR- and all-rac-alpha-tocopheryl acetate has primarily been based on human and animal studies using deuterium-labeled forms, whereby a higher biopotency of 2:1 (of RRR: all-rac) has been demonstrated, differing from the accepted biopotency ratio of 1.36:1. In agreement with previous studies, the 2S-forms exert very little importance for the vitamin E activity due to their limited bioavailability. We find notable differences between animal species with regard to the biodiscrimination between the 2R-forms. Especially, cows preferentially transfer RRR- alpha-tocopherol into the milk and blood system. The distribution of the stereoisomer forms varies from tissue to tissue, and in some cases, higher levels of the synthetic 2R-forms than of the RRR-form are obtained, for example, for rats. However, the biodiscrimination of the stereoisomers forms is influenced by other factors such as age, dietary levels, and time after dosage. More focus should be given on the bioactivity of the individual 2R-forms rather than just the comparison between RRR- and all-rac-alpha-tocopheryl acetate.
Topics: Animals; Antioxidants; Biological Availability; Humans; Species Specificity; Stereoisomerism; alpha-Tocopherol
PubMed: 17628178
DOI: 10.1016/S0083-6729(07)76010-7 -
Chemico-biological Interactions Oct 2021Acetylcholinesterase (AChE) is reversibly inhibited by α-tocopherol (α-T). Steady state kinetic analysis shows that α-T is a mixed slow-binding inhibitor of type A of...
Acetylcholinesterase (AChE) is reversibly inhibited by α-tocopherol (α-T). Steady state kinetic analysis shows that α-T is a mixed slow-binding inhibitor of type A of human enzyme (K = 0.49 μM; K = 1.6 μM) with a residence time of 2 min on target. Molecular dynamics (MD) simulations support this mechanism, and indicate that α-T first forms multiple non-specific interactions with AChE surface near the gorge entrance, then binds to the peripheral side with alkylene chain slowly sliding down the gorge, inducing no significant conformational change. α-T slightly modulates the progressive inhibition of AChE by the cyclic organophosphorus, cresyl saligenylphosphate, accelerating the fast pseudo-first order process of phosphorylation. A moderate accelerating effect of α-T on phosphorylation by paraoxon was also observed after pre-incubation of AChE in the presence of α-T. This accelerating effect of α-T on ex vivo paraoxon-induced diaphragm muscle weakness was also observed. The effect of α-T on AChE phosphylation was interpreted in light of molecular modeling results. From all results it is clear that α-T does not protect AChE against phosphylation by organophosphorus.
Topics: Acetylcholinesterase; Cholinesterase Inhibitors; Humans; Kinetics; Models, Molecular; Phosphorylation; Protein Conformation; alpha-Tocopherol
PubMed: 34506764
DOI: 10.1016/j.cbi.2021.109646 -
Molecular Vision 2009Vitamin E is an important natural antioxidant, and its most common and biologically active form is alpha-tocopherol. In addition to this, specific regulatory effects of... (Review)
Review
Vitamin E is an important natural antioxidant, and its most common and biologically active form is alpha-tocopherol. In addition to this, specific regulatory effects of vitamin E have been revealing. The body exerts a certain effort to regulate its tissue levels with specific tocopherol transport proteins and membrane receptors. Antiproliferative and protein kinase C-suppressing effects of alpha-tocopherol have been previously demonstrated, which have not been mimicked by beta-tocopherol or probucol. Protein kinase C promises to be an important area of interest in the means of glaucoma and cataractogenesis. It has been shown in different models that retinal vascular dysfunction due to hyperglycemia could be prevented by alpha-tocopherol via the diachylglycerol-protein kinase C pathway. Glutamate transporter activity has been shown to be modulated by protein kinase C. This pathway is also important in intraocular pressure-lowering effects of prostaglandin and its analogs in glaucoma therapy. Filtran surgery became another possible area of usage of alpha-tocopherol since its antiproliferative effect has been demonstrated in human Tenon's capsule fibroblasts. Prevention of posterior capsule opacification is another area for future studies. It is evident that when correct and safe modulation is the objective, alpha-tocopherol merits a concern beyond its mere antioxidant properties.
Topics: Animals; Antioxidants; Humans; Protein Kinase C; Signal Transduction; alpha-Tocopherol
PubMed: 19390643
DOI: No ID Found -
CNS Neuroscience & Therapeutics Jun 2022α-tocopherol showed antioxidant, anti-inflammatory and anti-apoptotic abilities in rat brain tissue, thus alleviating cerebral ischemia-reperfusion injury-induced nerve...
α-tocopherol showed antioxidant, anti-inflammatory and anti-apoptotic abilities in rat brain tissue, thus alleviating cerebral ischemia-reperfusion injury-induced nerve damage.
Topics: Animals; Antioxidants; Apoptosis; Brain Ischemia; Oxidative Stress; Rats; Reperfusion Injury; alpha-Tocopherol
PubMed: 35301808
DOI: 10.1111/cns.13814 -
Steroids Jan 2023The brain-specific cholesterol metabolite 24(S)-hydroxycholesterol (24S-OHC) has been shown to cause neuronal cell death when subjected to esterification by...
The brain-specific cholesterol metabolite 24(S)-hydroxycholesterol (24S-OHC) has been shown to cause neuronal cell death when subjected to esterification by acyl-CoA:cholesterol acyltransferase 1 (ACAT1). Accumulating 24S-OHC esters in the endoplasmic reticulum (ER) provoked ER membrane disruption and an integrated stress response (ISR), a signaling pathway that regulates adaptation to various stresses. We have previously reported that α-tocopherol (α-Toc) but not α-tocotrienol (α-Toc3), among vitamin E homologs, suppressed 24S-OHC-induced cell death without affecting ACAT1 activity in human neuroblastoma SH-SY5Y cells. However, the precise mechanisms underlying the inhibitory activity of α-Toc have yet to be elucidated. In the present study, we aimed to investigate the effects of α-Toc on the 24S-OHC-induced cell death machinery. We showed that α-Toc, but not α Toc3, suppressed 24S-OHC-induced ISR and downstream eukaryotic translation initiator factor 2α (eIF2α) phosphorylation. We also found that α-Toc inhibited stress granule formation and robust downregulation of nascent protein synthesis, which were induced by 24S-OHC treatment. Furthermore, disruption of ER membrane integrity was suppressed by α-Toc, but not by α-Toc3. Our findings suggest that the inhibitory effects of α-Toc on 24S-OHC-induced cell death may be attributed to its protective function against ER membrane disruption.
Topics: Humans; alpha-Tocopherol; Cell Death; Endoplasmic Reticulum; Hydroxycholesterols; Neuroblastoma
PubMed: 36351491
DOI: 10.1016/j.steroids.2022.109136 -
International Journal of Molecular... Aug 2023Aerobic organisms use molecular oxygen in several reactions, including those in which the oxidation of substrate molecules is coupled to oxygen reduction to produce... (Review)
Review
Aerobic organisms use molecular oxygen in several reactions, including those in which the oxidation of substrate molecules is coupled to oxygen reduction to produce large amounts of metabolic energy. The utilization of oxygen is associated with the production of ROS, which can damage biological macromolecules but also act as signaling molecules, regulating numerous cellular processes. Mitochondria are the cellular sites where most of the metabolic energy is produced and perform numerous physiological functions by acting as regulatory hubs of cellular metabolism. They retain the remnants of their bacterial ancestors, including an independent genome that encodes part of their protein equipment; they have an accurate quality control system; and control of cellular functions also depends on communication with the nucleus. During aging, mitochondria can undergo dysfunctions, some of which are mediated by ROS. In this review, after a description of how aging affects the mitochondrial quality and quality control system and the involvement of mitochondria in inflammation, we report information on how vitamin E, the main fat-soluble antioxidant, can protect mitochondria from age-related changes. The information in this regard is scarce and limited to some tissues and some aspects of mitochondrial alterations in aging. Improving knowledge of the effects of vitamin E on aging is essential to defining an optimal strategy for healthy aging.
Topics: Oxidative Stress; Reactive Oxygen Species; alpha-Tocopherol; Mitochondria; Oxygen; Vitamin E
PubMed: 37569829
DOI: 10.3390/ijms241512453 -
Molecular Nutrition & Food Research May 2010Vitamin E (alpha-tocopherol) has long been recognized as the major antioxidant in biological membranes, and yet many structurally related questions persist of how the... (Review)
Review
Vitamin E (alpha-tocopherol) has long been recognized as the major antioxidant in biological membranes, and yet many structurally related questions persist of how the vitamin functions. For example, the very low levels of alpha-tocopherol reported for whole cell extracts question how this molecule can successfully protect the comparatively enormous quantities of PUFA-containing phospholipids found in membranes that are highly susceptible to oxidative attack. The contemporary realization that membranes laterally segregate into regions of distinct lipid composition (domains), we propose, provides the answer. We hypothesize alpha-tocopherol partitions into domains that are enriched in polyunsaturated phospholipids, amplifying the concentration of the vitamin in the place where it is most needed. These highly disordered domains depleted in cholesterol are analogous, but organizationally antithetical, to the well-studied lipid rafts. We review here the ideas that led to our hypothesis. Experimental evidence in support of the formation of PUFA-rich domains in model membranes is presented, focusing upon docosahexaenoic acid that is the most unsaturated fatty acid commonly found. Physical methodologies are then described to elucidate the nature of the interaction of alpha-tocopherol with PUFA and to establish that the vitamin and PUFA-containing phospholipids co-localize in non-raft domains.
Topics: Biological Transport; Cell Membrane; Humans; Inflammation; Isomerism; LDL-Receptor Related Protein-Associated Protein; Liver; Phospholipid Transfer Proteins; Vitamin E; alpha-Tocopherol
PubMed: 20166146
DOI: 10.1002/mnfr.200900439 -
Canadian Journal of Physiology and... Nov 2023Avoiding hepatic steatosis is crucial for preventing liver dysfunction, and one mechanism by which this is accomplished is through synchronization of the rate of very...
Avoiding hepatic steatosis is crucial for preventing liver dysfunction, and one mechanism by which this is accomplished is through synchronization of the rate of very low density lipoprotein (VLDL) synthesis with its secretion. Endoplasmic reticulum (ER)-to-Golgi transport of nascent VLDL is the rate-limiting step in its secretion and is mediated by the VLDL transport vesicle (VTV). Recent in vivo studies have indicated that α-tocopherol (α-T) supplementation can reverse steatosis in nonalcoholic fatty liver disease, but its effects on hepatic lipoprotein metabolism are poorly understood. Here, we investigated the impact of α-T on hepatic VLDL synthesis, secretion, and intracellular ER-to-Golgi VLDL trafficking using an in vitro model. Pulse-chase assays using [H]-oleic acid and 100 µmol/L α-T demonstrated a disruption of early VLDL synthesis, resulting in enhanced apolipoprotein B-100 expression, decreased expression in markers for VTV budding, ER-to-Golgi VLDL transport, and reduced VLDL secretion. Additionally, an in vitro VTV budding assay indicated a significant decrease in VTV production and VTV-Golgi fusion. Confocal imaging of lipid droplet (LD) localization revealed a decrease in overall LD retention, diminished presence of ER-associated LDs, and an increase in Golgi-level LD retention. We conclude that α-T disrupts ER-to-Golgi VLDL transport by modulating the expression of specific proteins and thus reduces VLDL secretion.
Topics: Humans; Lipoproteins, VLDL; alpha-Tocopherol; Liver; Transport Vesicles; Fatty Liver; Endoplasmic Reticulum; Triglycerides
PubMed: 37683292
DOI: 10.1139/cjpp-2023-0086 -
Free Radical Biology & Medicine Jul 2007The inability of other antioxidants to substitute for alpha-tocopherol in a number of cellular reactions, the lack of a compensatory antioxidant response in the gene... (Review)
Review
The inability of other antioxidants to substitute for alpha-tocopherol in a number of cellular reactions, the lack of a compensatory antioxidant response in the gene expression under conditions of alpha-tocopherol deficiency, the unique uptake of alpha-tocopherol relative to the other tocopherols and its slower catabolism, and the striking differences in the molecular function of the different tocopherols and tocotrienols, observed in vitro, unrelated to their antioxidant properties, are all data in support of a nonantioxidant molecular function of alpha-tocopherol. Furthermore, in vivo studies have also shown that alpha-tocopherol is not able, at physiological concentrations, to protect against oxidant-induced damage or prevent disease allegedly caused by oxidative damage. Alpha-tocopherol appears to act as a ligand of not yet identified specific proteins (receptors, transcription factors) capable of regulating signal transduction and gene expression.
Topics: Animals; Antioxidants; DNA; Humans; Membrane Lipids; Oxidative Stress; Phospholipids; alpha-Tocopherol
PubMed: 17561089
DOI: 10.1016/j.freeradbiomed.2007.03.013 -
Food Chemistry Sep 2021The interaction between antioxidants is affected by many factors, such as concentration, ratio and system. In this study, different concentrations of α-tocopherol and...
The interaction between antioxidants is affected by many factors, such as concentration, ratio and system. In this study, different concentrations of α-tocopherol and γ-oryzanol showed antagonistic effect in the oil-in-water emulsion, and the distribution of α-tocopherol increased in aqueous phase after combined with γ-oryzanol. The concentration could affect the degree of antagonism. According to fluorescence quenching, cyclic voltammetry measurements and the oxidative decomposition of antioxidants during storage, the inhibitory effect of γ-oryzanol on the regeneration of α-tocopherol was proposed to be responsible for the antagonism. This work can provide suggestions for studying the mechanism of antioxidant interaction in emulsion system.
Topics: Antioxidants; Emulsions; Oxidation-Reduction; Phenylpropionates; Water; alpha-Tocopherol
PubMed: 33819788
DOI: 10.1016/j.foodchem.2021.129648