Vitamin E: a sensor and an information transducer of the cell oxidation state

Azzi, Angelo; Boscoboinik, Daniel; Marilley, D.; Özer, Nesrin Kartal; Stäuble, Barbara; Tasinato, Andrea

doi:10.1093/ajcn/62.6.1337s

Cited by 134 publications

(52 citation statements)

References 73 publications

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“…At 25-50 M, ␣-tocopherol is known to regulate signal transduction pathways by mechanisms that are independent of its antioxidant properties (9,10). This study provides the first evidence describing a signal transduction regulatory role of tocotrienol.…”

Section: Discussionmentioning

confidence: 69%

“…At concentrations 25-50 M, ␣-tocopherol is known to regulate signal transduction pathways by mechanisms that are independent of its antioxidant properties. ␣-Tocopherol, but not ␤-tocopherol having comparable antioxidant properties, inhibited inducible protein kinase C activity in smooth muscle cells (9,10). The signal transduction regulatory properties of tocotrienols, however, are yet unknown.…”

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confidence: 94%

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Molecular Basis of Vitamin E Action

Sen

Khanna

Roy

et al. 2000

Journal of Biological Chemistry

279

113

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HT4 hippocampal neuronal cells were studied to compare the efficacy of tocopherols and tocotrienol to protect against glutamate-induced death. Tocotrienols were more effective than ␣-tocopherol in preventing glutamate-induced death. Uptake of tocotrienols from the culture medium was more efficient compared with that of ␣-tocopherol. Vitamin E molecules have potent antioxidant properties. Results show that at low concentrations, tocotrienols may have protected cells by an antioxidant-independent mechanism. Examination of signal transduction pathways revealed that protein tyrosine phosphorylation processes played a central role in the execution of death. Activation of pp60 c-Src kinase and phosphorylation of ERK were observed in response to glutamate treatment. Nanomolar amounts of ␣-tocotrienol, but not ␣-tocopherol, blocked glutamate-induced death by suppressing glutamate-induced early activation of c-Src kinase. Overexpression of kinase-active cSrc sensitized cells to glutamate-induced death. Tocotrienol treatment prevented death of Src-overexpressing cells treated with glutamate. ␣-Tocotrienol did not influence activity of recombinant c-Src kinase suggesting that its mechanism of action may include regulation of SH domains. This study provides first evidence describing the molecular basis of tocotrienol action. At a concentration 4 -10-fold lower than levels detected in plasma of supplemented humans, tocotrienol regulated unique signal transduction processes that were not sensitive to comparable concentrations of tocopherol.

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Section: Discussionmentioning

confidence: 69%

mentioning

confidence: 94%

Molecular Basis of Vitamin E Action

Sen

Khanna

Roy

et al. 2000

Journal of Biological Chemistry

279

113

View full text Add to dashboard Cite

show abstract

“…For example, some of the anti-atherosclerotic effects of vitamin E have been ascribed to non-antioxidant effects such as regulation of transcription of cytokines and growth factors (Azzi et al, 1995), improvement of endothelial-dependent vasodilatation (Paolisso, 2000) and platelet…”

Section: Dietary Antioxidants In Diabetes Mellitusmentioning

confidence: 99%

Oxidative stress status in patients with diabetes mellitus: relationship to diet

et al. 2003

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Objective: To investigate the relationship between dietary intakes and in vivo oxidative stress (OS) status in diabetic patients. Design: Case-control study. Setting: Outpatient-Clinic and Laboratory Endocrinology, University Antwerp. Subjects and methods: A total of 30 patients (24 type 1 diabetes mellitus (T1DM)/6 type 2 diabetes mellitus (T2DM) were asked to complete a 2 weekdays+1weekend day food consumption questionnaire during the week preceding their yearly diabetes control consultation, when samples were collected for the assay of oxidative stress (OS) (blood levels of antioxidants, peroxides, malondialdehyde (MDA) and minerals). Blood samples were also collected from 25 age-and sex-matched healthy controls. Results: Diabetic patients had lower glutathione (5.8071.15 vs 6.7571.03 mmol/g Hb in the controls, P ¼ 0.002) and higher MDA (0.68770.212 vs 0.54570.101 mmol/l, P ¼ 0.002). Although the group average intakes were within the Belgian RDA, intakes of fat 435% energy, fibre o15 g/1000 kcal, fruit o2 portions and vitamin E o10 mg/day were seen in more than 20 patients. Blood antioxidants did not correlate with intakes of energy, fat, protein or fibres or of their respective antioxidant. Vitamins A and E correlated with serum lipids (r ¼ 0.58, P o0.0005 between serum a-tocopherol and cholesterol). Blood peroxide levels were only related to intakes of saturated fat and cholesterol (Po0.05). In diabetic subjects but not in controls (Po0.05) MDA was related to glutathione and uric acid. Conclusions: In diabetic patients, blood levels of antioxidants are not related to their dietary intakes but to serum lipids. Levels of oxidative damage products are only related to intakes of saturated fats and cholesterol and to levels of endogenous antioxidants.

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“…Following supplementation to humans, the level of ␣-tocotrienol in the plasma has been estimated to be 1 M (7). At concentrations of 25-50 M, ␣-tocopherol is known to regulate signal transduction pathways by mechanisms that are independent of its antioxidant properties (8,9). Micromolar amounts of tocotrienol, but not tocopherol, have been shown to suppress the activity of hydroxy-3-methylglutaryl-coenzyme A reductase (10,11).…”

mentioning

confidence: 99%

Molecular Basis of Vitamin E Action

Khanna

Roy

Ryu

et al. 2003

Journal of Biological Chemistry

261

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Vitamin E is a generic term for tocopherols and tocotrienols. This work is based on our striking evidence that, in neuronal cells, nanomolar concentrations of ␣-tocotrienol, but not ␣-tocopherol, block glutamate-induced death by suppressing early activation of c-Src kinase (Sen, C. K., Khanna, S., Roy, S., and Packer, L. (2000) J. Biol. Chem. 275, 13049 -13055). This study on HT4 and immature primary cortical neurons suggests a central role of 12-lipoxygenase (12-LOX) in executing glutamate-induced neurodegeneration. BL15, an inhibitor of 12-LOX, prevented glutamate-induced neurotoxicity. Moreover, neurons isolated from 12-LOX-deficient mice were observed to be resistant to glutamate-induced death. In the presence of nanomolar ␣-tocotrienol, neurons were resistant to glutamate-, homocysteine-, and L-buthionine sulfoximine-induced toxicity. Long-term time-lapse imaging studies revealed that neurons and their axo-dendritic network are fairly motile under standard culture conditions. Such motility was arrested in response to glutamate challenge. Tocotrienol-treated primary neurons maintained healthy growth and motility even in the presence of excess glutamate. The study of 12-LOX activity and metabolism revealed that this key mediator of glutamate-induced neurodegeneration is subject to control by the nutrient ␣-tocotrienol. In silico docking studies indicated that ␣-tocotrienol may hinder the access of arachidonic acid to the catalytic site of 12-LOX by binding to the opening of a solvent cavity close to the active site. These findings lend further support to ␣-tocotrienol as a potent neuroprotective form of vitamin E.

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Vitamin E: a sensor and an information transducer of the cell oxidation state

Cited by 134 publications

References 73 publications

Molecular Basis of Vitamin E Action

Molecular Basis of Vitamin E Action

Oxidative stress status in patients with diabetes mellitus: relationship to diet

Molecular Basis of Vitamin E Action

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