Regulation of gene expression by α-tocopherol

Azzi, Angelo; Gysin, René; Kempná, Petra; Munteanu, Adelina; Villacorta, Luis; Visarius, Theresa; Zingg, Jean Marc

doi:10.1515/bc.2004.072

Cited by 128 publications

(83 citation statements)

References 45 publications

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“…Suppression of T 3 -induced gene expression by α-tocopherol and NAC, antioxidants having different mechanisms of action, strengthens the contention that the underlying mechanisms are oxidant dependent (Macdonald et al, 2003). In this context, non-antioxidant ligand-induced effects on specific proteins have been proposed to mediate cell signaling and regulation of gene expression by α-tocopherol (Azzi et al, 2004). However, the latter non-antioxidant mechanism is not imitated by structurally related (γ-tocopherol) or unrelated (NAC) antioxidants (Azzi et al, 2004) and its relationship with the redox activation of signaling cascades has not been established.…”

Section: Redox Regulation Of Gene Expression By Thyroid Hormonementioning

confidence: 65%

“…In this context, non-antioxidant ligand-induced effects on specific proteins have been proposed to mediate cell signaling and regulation of gene expression by α-tocopherol (Azzi et al, 2004). However, the latter non-antioxidant mechanism is not imitated by structurally related (γ-tocopherol) or unrelated (NAC) antioxidants (Azzi et al, 2004) and its relationship with the redox activation of signaling cascades has not been established. Finally, the finding that the mRNA expression of two target proteins of TH action, namely, mitochondrial glycerol-3-phosphate dehydrogenase and the adenine nucleotide translocator 2, is not modified by α-tocopherol and NAC (Videla et al, 2007), suggests that redox regulation of gene transcription by T 3 is a secondary mechanism to those triggered by genomic pathways (Fig.…”

Section: Redox Regulation Of Gene Expression By Thyroid Hormonementioning

confidence: 99%

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The role of thyroid hormone calorigenesis in the redox regulation of gene expression

et al. 2006

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Thyroid hormone (TH; 3,3 , ,5-triiodothyronine, T 3 ) is required for the normal function of most tissues, with major effects on O 2 consumption and metabolic rate. These are due to transcriptional activation of respiratory genes through the interaction of T 3 -liganded TH receptors with TH response elements or the activation of intermediate factors, with the consequent higher production of reactive O 2 species (ROS) and antioxidant depletion. T 3 -induced oxidative stress in the liver triggers the redox upregulation of the expression of cytokines (tumor necrosis factor-α [TNF-α], interleukin-10), enzymes (inducible nitric oxide synthase, manganese superoxide dismutase), and anti-apoptotic proteins (Bcl-2), via a cascade initiated by TNF-α produced by Kupffer cells, involving inhibitor of κB phosphorylation and nuclear factor-κB activation. Thus, TH calorigenesis triggers an expression pattern that may represent an adaptive mechanism to re-establish redox homeostasis and promote cell survival under conditions of ROS toxicity secondary to TH-induced oxidative stress. Mechanisms of expression of respiratory and redox-sensitive genes may be functionally integrated, which could be of importance to understand the complexities of TH action and the outcome of thyroid gland dysfunction.

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Section: Redox Regulation Of Gene Expression By Thyroid Hormonementioning

confidence: 65%

Section: Redox Regulation Of Gene Expression By Thyroid Hormonementioning

confidence: 99%

The role of thyroid hormone calorigenesis in the redox regulation of gene expression

et al. 2006

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“…by direct redox cycling) instead of by altering ROS produced by the mitochondrial electron transport chain, a series of experiments were performed. Using increasing concentrations of ␣-tocopherol in a superoxide-generating system (hypoxanthine/xanthine oxidase), we failed to observe enhanced superoxide production by EPR, and in fact, ␣-tocopherol decreased the superoxide signal in a dose-dependent manner, 5 as expected and as previously reported (35). Thus, our data support an effect of ␣-tocopherol on mitochondrial superoxide production when ␣-tocopherol is extremely depleted, but as levels increase, this response is reversed.…”

Section: Brain ␣-Tocopherol Levels In Ved and Ttpmentioning

confidence: 76%

Prolonged α-Tocopherol Deficiency Decreases Oxidative Stress and Unmasks α-Tocopherol-dependent Regulation of Mitochondrial Function in the Brain

Cuddihy

Ali

Musiek

et al. 2008

Journal of Biological Chemistry

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Vitamin E is the major lipid-soluble chain-breaking antioxidant in mammals and plays an important role in normal development and physiology. Deficiency (whether dietary or genetic) results in primarily nervous system pathology, including cerebellar neurodegeneration and progressive ataxia (abnormal gait). However, despite the widely acknowledged antioxidant properties of vitamin E, only a few studies have directly correlated levels of reactive oxygen species with vitamin E availability in animal models. We explored the relationship between vitamin E and reactive oxygen species in two mouse models of vitamin E deficiency: dietary deficiency and a genetic model (tocopherol transfer protein, Ttp ؊/؊ mice). Both groups of mice developed nearly complete depletion of ␣-tocopherol (the major tocopherol in vitamin E) in most organs, but not in the brain, which was relatively resistant to loss of ␣-tocopherol. F4-neuroprostanes, an index of lipid peroxidation, were unexpectedly lower in brains of deficient mice compared with controls. In vivo oxidation of dihydroethidium by superoxide radical was also significantly lower in brains of deficient animals. Superoxide production by brain mitochondria isolated from vitamin E-deficient and Ttp ؊/؊ mice, measured by electron paramagnetic resonance spectroscopy, demonstrated a biphasic dependence on exogenously added ␣-tocopherol. At low concentrations, ␣-tocopherol enhanced superoxide flux from mitochondria, a response that was reversed at higher concentrations. Here we propose a mechanism, supported by molecular modeling, to explain decreased superoxide production during ␣-tocopherol deficiency and speculate that this could be a beneficial response under conditions of ␣-tocopherol deficiency.␣-Tocopherol was first discovered as a micronutrient indispensable for reproduction in female rats (1). The view that ␣-tocopherol functions solely as a chain-breaking antioxidant has prevailed, reflecting a large body of accumulated experimental evidence showing that ␣-tocopherol can reduce lipid peroxidation in many models and the observation that ␣-tocopherol inhibits lipid peroxidation by scavenging peroxyl radicals faster (10 6 M Ϫ1 s Ϫ1 ) than they can react with other lipids (ϳ10 2 M Ϫ1 s Ϫ1 ) or proteins (2). Recently, however, a broad array of "nonantioxidant" cellular functions for ␣-tocopherol have emerged (reviewed in Refs. 3-8, but see Ref. 9 for the opposing view that supports a pure antioxidative function for ␣-tocopherol). The mechanism by which these "nonantioxidant" actions factor into the observed biological effects of ␣-tocopherol is not yet known. A systematic study of the relationship between levels of ␣-tocopherol and ROS 4 production is one approach to begin to differentiate the documented ability of ␣-tocopherol to act as a lipid peroxidation inhibitor and antioxidant versus its other potential activities in vivo.In the current study, we used two mouse models of vitamin E deficiency: 1) dietary deficiency (VED) in C57BL6 mice and 2) a genetic model, ␣-tocopherol tra...

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“…For example, vitamin E inhibits protein kinase C activity, which has been associated with insulin resistance experimentally [19]. Vitamin E regulates several genes; for example, it upregulates the expression of PPARG, the gene for peroxisome proliferator activated receptor γ (PPARγ) [20]. PPARγ is a nuclear receptor the stimulation of which improves glucose tolerance and insulin sensitivity in type 2 diabetes mellitus patients and in animal models of insulin resistance [21].…”

Section: Discussionmentioning

confidence: 99%

Effect of α-tocopherol and β-carotene supplementation on the incidence of type 2 diabetes

Kataja-Tuomola¹,

Sundell²,

Männistö³

et al. 2007

Diabetologia

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Aims/hypothesis Type 2 diabetes is associated with reduced antioxidant defence. Only a few human studies have investigated the role of antioxidants in the pathogenesis of diabetes. This study aimed to examine whether α-tocopherol or β-carotene affected the occurrence of type 2 diabetes. Methods In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, controlled trial, 29,133 male smokers aged 50-69 years were randomised to receive either α-tocopherol (50 mg/day) or β-carotene (20 mg/day) or both agents or placebo daily for 5-8 years (median 6.1 years). Baseline serum samples were analysed for α-tocopherol and β-carotene using HPLC. Cases of diabetes were identified from a nationwide Finnish registry of patients receiving drug reimbursement for diabetes. Of 27,379 men without diabetes at baseline, 705 men were diagnosed with diabetes during the follow-up of up to 12.5 years. Results Baseline serum levels of α-tocopherol and β-carotene were not associated with the risk of diabetes in the placebo group: the relative risk (RR) between the highest and lowest quintiles of α-tocopherol was 1.59 (95% CI 0.89-2.84) and that for β-carotene was 0.66 (95% CI 0.40-1.10). Neither supplementation significantly affected the incidence of diabetes: the RR was 0.92 (95% CI 0.79-1.07) for participants receiving α-tocopherol compared with nonrecipients and 0.99 (95% CI 0.85-1.15) for participants receiving β-carotene compared with non-recipients. Conclusions/interpretation Neither α-tocopherol nor β-carotene supplementation prevented type 2 diabetes in male smokers. Serum levels of α-tocopherol and β-carotene were not associated with the risk of type 2 diabetes.ClinicalTrials.gov ID no. NCT00342992

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Regulation of gene expression by α-tocopherol

Abstract: Several genes are regulated by tocopherols which can be categorized, based on their function, into five groups: genes that are involved in the uptake and degradation of tocopherols (Group

Cited by 128 publications

References 45 publications

The role of thyroid hormone calorigenesis in the redox regulation of gene expression

The role of thyroid hormone calorigenesis in the redox regulation of gene expression

Prolonged α-Tocopherol Deficiency Decreases Oxidative Stress and Unmasks α-Tocopherol-dependent Regulation of Mitochondrial Function in the Brain

Effect of α-tocopherol and β-carotene supplementation on the incidence of type 2 diabetes

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