Specific Cellular Responses to α-Tocopherol

Azzi, Angelo; Breyer, Isabel; Feher, Maria; Pastori, Mariella; Ricciarelli, Roberta; Spycher, Stefan; Staffieri, Mariagrazia; Stocker, Achim; Zimmer, Sabine; Zingg, Jean‐Marc

doi:10.1093/jn/130.7.1649

Cited by 137 publications

(90 citation statements)

References 68 publications

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“…The fact that other antioxidants, even β-tocopherol, do not inhibit PKC suggests that these mechanisms are not related to the anti-oxidant effect of vitamin E [32]. The inhibitory effect of α-tocopherol (VitE) on PKC activation is concordant with its effect on phosphorylation of the myristolated, alaninerich C kinase substrate protein, a substrate of PKC [25], and with the fact that it also increased protein phosphatase type 2A activity, which results in PKCdephosphorylation [32]. These observations suggest that a ligand/receptor type of mechanism is the basis of the action of VitE on PKC.…”

Section: Discussionmentioning

confidence: 99%

Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-β in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats

et al. 2004

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Aims/hypothesis. The impact of early vitamin E supplementation on vascular function in diabetes remains unresolved. Therefore, we examined the effects of vitamin E on functional and structural parameters and on chemical markers that are disturbed in diabetes in mesenteric and femoral arteries. Methods. Segments of both arteries, taken from control and 8-week-old streptozotocin diabetic Wistar rats that were treated or not with vitamin E, were mounted on wire and pressure myographs, after which endothelium-dependent and -independent vasodilation was assessed. Passive mechanical wall properties and the localisation and levels of protein kinase C (PKC)-β 2 and AGE were evaluated in these vessels. Results. Vitamin E supplementation was associated with improved endothelium-dependent and -independent vasodilatation in mesenteric arteries from diabetic rats. Impaired endothelium-dependent vasodilatation in diabetic mesenteric vessels was associated with PKC-β 2 up-regulation and this was prevented by vitamin E supplementation. Increased AGE accumulation and plasma isoprostane levels in diabetic rats were not changed by vitamin E. In the femoral artery, vitamin E supplementation had no effect on endothelium-dependent or -independent vasodilatation, but did prevent the wall stiffening associated with diabetes. Conclusions/interpretation. Early vitamin E supplementation has a beneficial effect on diabetes-induced endothelial dysfunction in resistance arteries. This benefit may arise from a direct effect on smooth muscle function, as a result of inhibition of the PKC-β 2 isoform by vitamin E. Abbreviations: ACh, acetylcholine · EDHF, endothelium-derived hyperpolarising factor · GHb, glycohaemoglobin · h, wall thickness · ID, internal diameter · L, length · l-NAME, N ω -nitro-L-arginine methyl ester · NO, nitric oxide · OD, outside diameter · P, intraluminal pressure · PKC, protein kinase C · PSS, physiological saline solution · SNP, sodium nitroprusside · STZ, streptozotocin · VitE, vitamin E supplementation · V max , maximal relaxation

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Section: Discussionmentioning

confidence: 99%

Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-β in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats

et al. 2004

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“…For example, vitamin E inhibits protein kinase C by a nonantioxidant mechanism (25). Vitamin E also accelerates diacylglycerol kinase activity, thereby decreasing levels of diacylglycerol, which is an allosteric activator of protein kinase C (26). Increased protein kinase C activity apparently impairs insulin action by phosphorylating serine or threonine residues on insulin receptor and insulin receptor substrate-1 proteins (27).…”

Section: Statisticsmentioning

confidence: 99%

Effect of High-Dose Vitamin E on Insulin Resistance and Associated Parameters in Overweight Subjects

et al. 2004

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OBJECTIVE -Markers of oxidative stress and plasma alanine transferase (ALT) levels are increased and circulating antioxidant concentrations are reduced in individuals with insulin resistance. Vitamin E improves glycemic control in people with diabetes. We tested the hypothesis that vitamin E would decrease markers of oxidative stress and plasma ALT levels and improve insulin sensitivity in overweight individuals. RESEARCH DESIGN AND METHODS -Eighty overweight individuals (BMI Ͼ27 kg/m2 ) were randomly allocated to receive either 800 IU vitamin E per day or a matching placebo for 3 months. The dose of vitamin E was increased to 1,200 IU per day for a further 3 months.RESULTS -Plasma peroxides decreased by 27% at 3 months and by 29% at 6 months in the group that received vitamin E and were positively correlated with plasma vitamin E concentrations at the 6-month time point. At 3 months, fasting plasma glucose and insulin concentrations were significantly reduced and homeostasis model assessment increased. These changes were not apparent at 6 months. Plasma ALT concentrations declined significantly throughout the study period.CONCLUSIONS -In conclusion, these findings indicate that vitamin E improves oxidative stress and hepatocellular function. Although insulin resistance also improves, this effect appears transient. Diabetes Care 27:2166 -2171, 2004T he prevalence of diabetes is increasing dramatically in the western world (1). This increase parallels that of obesity, with insulin resistance explaining the link between these two entities (2). Although the precise mechanism responsible for insulin resistance remains unclear, it would appear that a number of adipocyte-derived factors impair insulin activity and that the secretion of these factors is altered in the obese individual (3). Diabetes results when, in addition to insulin resistance, ␤-cell dysfunction occurs, leading to relative insulin deficiency. Interventions shown to be effective at preventing the progression to diabetes include lifestyle modification (4,5) and certain pharmacologic agents (4,6).One of the adipocyte-derived factors implicated in the pathogenesis of insulin resistance is the free fatty acid (FFA) (7). Although the rate of release of FFAs from individual adipocytes may not be raised in obesity, the increased amount of adipose tissue overall leads to an increase in the flux of FFAs to the liver and skeletal muscle, the two tissues most intimately involved in glucose handling (8). Once FFAs enter target tissues, they are either stored as triglycerides or are utilized as a substrate for oxidation by the cell's mitochondria. As a result of the normal process of oxidation, reactive oxygen species (ROS) are produced (9). These ROS are potentially harmful to cellular functions. To prevent these harmful effects, the cell has developed a complex antioxidant system to dispose of ROS. However, antioxidant concentrations are reduced in obese individuals, and the resulting imbalance between the production of ROS and antioxidant defenses results in o...

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“…This latter ability to stabilize membranes may help to prevent the damaging actions of phospholipases, although this is still under debate (6)(7)(8)(9)(10). ␣ -T has also been shown to inhibit protein kinase C (11)(12)(13), apparently without directly binding to the enzyme but rather by activating the translocation of the protein phosphatase 2A to the plasma membrane (14). These and other observations, such as those of the effect of ␣ -T on diacylglycerol (DAG) kinase (15,16), CoA-independent transacylase (17), and phospholipase D (18) suggest that the modulation of enzyme activity may have more to do with the effect tocopherol has on membrane structure, particularly inasmuch as all these enzymes act on substrates that are in membranes or are activated/inhibited when translocated to a membrane surface.…”

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confidence: 99%

The effect of vitamin E on the structure of membrane lipid assemblies

Bradford

Atkinson

Fuller

et al. 2003

Journal of Lipid Research

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The effects of vitamin E on the activity of membrane-dependent enzymes suggest that it acts indirectly by modifying some properties of the lipid host. The effects of ␣ -tocopherol ( ␣ -T) and ␣ -tocopherol hemisuccinate ( ␣ -THS) on phospholipid monolayer structure, curvature, and bending elasticity were examined using X-ray diffraction and the osmotic stress method. These ligands were mixed with the hexagonal phase-forming lipid, dioleoylphosphatidylethanolamine (DOPE). Increasing levels up to 50 mol% ␣ -T in DOPE in excess water result in a systematic decrease in the lattice dimension. Analysis of the structural changes imposed by ␣ -T shows that it contributes a spontaneous radius of curvature of ؊ 13.7 Å. This unusually negative value is comparable to diacylglycerols. ␣ -T does not affect the bending elasticity of these monolayers. ␣ -THS in its charged form decreases membrane curvature, but in its undissociated neutral form has a qualitatively similar but reduced effect on monolayer curvature, as does ␣ -T. We discuss these results in terms of the local stresses such ligands would produce in the vicinity of a membrane protein, and how one might expect proteins to respond to such stress.

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Specific Cellular Responses to α-Tocopherol

Cited by 137 publications

References 68 publications

Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-β in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats

Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-β in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats

Effect of High-Dose Vitamin E on Insulin Resistance and Associated Parameters in Overweight Subjects

The effect of vitamin E on the structure of membrane lipid assemblies

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