Vitamin E Regulation of Mitochondrial Superoxide Generation

Chow, Ching K.

doi:10.1159/000046879

Cited by 48 publications

(28 citation statements)

References 104 publications

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“…Recent studies indicate that Á-tocopherol may be important in prevention of human disease [30]. ·-Tocopherol reacts with superoxide and peroxyl radicals to form ·-tocopheroxyl radical [31]. Reduced coenzyme Q 10 regenerates ·-tocopherol from tocopheroxyl radical, thereby maintaining adequate concentrations of vitamin E [32].…”

Section: Discussionmentioning

confidence: 99%

Lipid-Soluble Antioxidants and Pregnancy: Maternal Serum Levels of Coenzyme Q<sub>10</sub>, α-Tocopherol and γ-Tocopherol in Preeclampsia and Normal Pregnancy

Palan

Shaban

Martino

et al. 2004

Gynecol Obstet Invest

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It has been hypothesized that in preeclampsia, the antioxidant-deficient state may facilitate increased attacks of free radicals, which may result in endothelial cell damage. The purpose of this study was to investigate the association of three lipid-soluble antioxidants, coenzyme Q₁₀, α-tocopherol and γ-tocopherol, with preeclampsia and normal pregnancy. Serum levels of all three antioxidants in 42 women with normal pregnancies, 25 with mild preeclampsia and 28 with severe preeclampsia were measured by high-pressure liquid chromatography. A significant decrease was observed in serum levels of coenzyme Q₁₀ and α-tocopherol (p < 0.001 for each by the Kruskal-Wallis rank test) in women with preeclampsia compared to levels in normal pregnancy. γ-Tocopherol levels were comparable among the different groups. Logistic regression analysis revealed significant association between grades of preeclampsia and both serum coenzyme Q₁₀ and α-tocopherol levels (p = 0.000 and 0.030, respectively). Coenzyme Q₁₀ and α-tocopherol are potent antioxidants, and the decreased levels of these two antioxidants in preeclampsia may alter the normal redox balance, thereby reducing the ability of antioxidant defenses to protect against free radical damage. This could be a factor in the endothelial cell damage observed in preeclampsia.

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Section: Discussionmentioning

confidence: 99%

Lipid-Soluble Antioxidants and Pregnancy: Maternal Serum Levels of Coenzyme Q<sub>10</sub>, α-Tocopherol and γ-Tocopherol in Preeclampsia and Normal Pregnancy

Palan

Shaban

Martino

et al. 2004

Gynecol Obstet Invest

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“…Similarly, the rate of superoxide generation by submitochondrial particles was found to inversely related to the vitamin E content in skeletal muscle, liver, and kidney of mice [44]. These findings suggest that dietary vitamin E may mediate the generation and/or level of superoxide and related ROS/RNS via maintaining mitochondrial integrity and stability, mediating the superoxide generation systems, and/or scavenging superoxide generated [43,45].…”

Section: How May Vitamin E Protect Against Oxi-dative Damage?mentioning

confidence: 76%

Antioxidant Function and Health Implications of Vitamin E

Chow¹,

Chow-Johnson²

2013

TONUTRJ

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Superoxide, a key precursor of important reactive oxygen/nitrogen species (ROS/RNS), may release iron from its protein complex. By mediating the generation and/level of superoxide, vitamin E, the most important fat-soluble antioxidant and free radical scavenger, may exert its antioxidant function by limiting the formation of reactive hydroxyl radicals and peroxynitrite. The antioxidant function of vitamin E is augmented by GSH peroxidase and related metabolic systems which respond adaptively and compensatively to oxidative stress. By mediating the levels of ROS/RNS, vitamin E may also modulate the activation and/or expression of redox-sensitive biological response modifiers, and thereby attenuate the cellular events leading to the onset and development of aging and other degenerative disorders. Earlier epidemiological data and retrospective studies show an association between increased intake of vitamin E and reduced risk of cardiovascular disease, cancer, and other disorders. However, subsequent prospective randomized placebo-controlled studies and interventional trials have provided inconsistent findings. Data available from recent large-scale interventional trials suggest that vitamin E supplements at high doses are not beneficial.Keywords: Vitamin E, tocopherols, superoxide, biological function, health benefit. INTRODUCTIONVitamin E is referred to all tocol (tocopherol) and tocotrienol derivatives qualitatively exhibiting the biological activity of RRR-α-tocopherol. There are four tocopherols (α-, β-, γ-and δ-) and four tocotrienols (α-, β-, γ-and δ-) that occur naturally, differing in the number and position of methyl groups on the chroman ring [1,2]. Vitamin E was discovered 90 years ago, and a number of species-dependent and organ-specific deficiency symptoms of vitamin E were reported later [3,4]. However, due to the lack of clinically defined deficient syndromes attributable to vitamin E and the difficult to produce vitamin E deficiency in adults, its essentiality for humans was established only after the discovery of α-tocopherol transfer protein decades later [2,[5][6][7][8]. The transfer protein binds RRR-α-tocopherol preferentially over other forms/isomers of tocopherols, and enhances its transfer and return to the liver. The presence of α-tocopherol transfer protein is largely responsible for higher biological activity of RRR-α-form than other forms/isomers.

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“…Hence, insights into the topology of the enzyme in relation to the respiratory chain are crucial for understanding regulatory mechanisms of NO action. It has been reported that 5% of the oxygen consumed by the mitochondrial respiratory chain is converted into superoxide (29). The formed superoxide reacts with NO or could be converted to hydrogen peroxide (catalyzed by Mn-SOD, 10 9 mol/liter Ϫ1 s Ϫ1 ; spontaneously, 10 5 mol/liter Ϫ1 s Ϫ1 ) (30).…”

Section: Discussionmentioning

confidence: 99%

Docking of Endothelial Nitric Oxide Synthase (eNOS) to the Mitochondrial Outer Membrane

Gao

Chen

Brodsky

et al. 2004

Journal of Biological Chemistry

112

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Despite growing evidence for a mitochondrial localization of nitric oxide (NO) synthase and a broadening spectrum of NO actions on mitochondrial respiration and apoptosis, the basis for interaction between the enzyme and the organelle remain obscure. Here we investigated mitochondrial localization of endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells and human embryonic kidney cells transfected or infected with eNOS expression vectors. Copurification of eNOS with mitochondria was observed in both human umbilical vein endothelial cells and eNOSexpressing human embryonic kidney cells. Immunodetectable eNOS was cleaved from mitochondria by proteinase K treatment, suggesting eNOS association with the outer mitochondrial membrane. Localization of eNOS to a proteinase K-cleavable site on the cytoplasmic face of the outer membrane was confirmed by immunogold labeling of non-permeabilized mitochondria. Markers for mitochondrial subfractions ruled out the possibility of eNOS association with an intramitochondrial site or inverted mitochondrial particles. Denaturation of eNOS did not attenuate association with mitochondria. Mutant eNOS lacking a pentabasic amino acid sequence within the autoinhibitory domain (residues 628 -632 of the bovine eNOS) showed dramatically reduced binding to the mitochondrial but not to the plasma membrane, which was associated with increased oxygen consumption. Collectively, these findings argue in favor of eNOS localization to the outer mitochondrial membrane in endothelial cells and identify elements of a novel anchoring mechanism.An association of NOS-like proteins with mitochondria has previously been demonstrated immunohistochemically (1-4). Further supporting evidence was provided by the partial purification of mitochondrial nitric oxide synthase (mtNOS) 1 activity (5, 6). There is an ongoing debate as to the identity of mtNOS; immunologic cross-reaction of mtNOS with antibodies against endothelial NOS (eNOS) (1, 3, 7), neuronal NOS (4), and inducible NOS (6) have been reported. A recent investigation (8) has identified a neuronal NOS in cardiomyocyte mitochondria. It has been suggested that mtNOS plays important roles in oxidative stress and apoptosis (9, 10), regulation of mitochondrial respiration (11,12), and modulation of intracellular Ca 2ϩ homeostasis (13).The potential distribution of mtNOS in subfractions of mitochondria has been explored but remains enigmatic. Some indirect evidence suggests that mtNOS is localized to the inner mitochondrial membrane. Indeed, immunohistochemical findings suggest that mtNOS co-localizes with succinate dehydrogenase, a mitochondrial marker for the inner membrane (2). Further support for an inner membrane localization of NOS in mitochondria came from NOS activity assays, which indicated that specific activity in submitochondrial particles and crude fractions was higher than that of mitochondrial homogenates or permeabilized mitochondria (14). In contrast, a recent report (15) suggested that eNOS localizes to the oute...

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Vitamin E Regulation of Mitochondrial Superoxide Generation

Cited by 48 publications

References 104 publications

Lipid-Soluble Antioxidants and Pregnancy: Maternal Serum Levels of Coenzyme Q<sub>10</sub>, α-Tocopherol and γ-Tocopherol in Preeclampsia and Normal Pregnancy

Lipid-Soluble Antioxidants and Pregnancy: Maternal Serum Levels of Coenzyme Q<sub>10</sub>, α-Tocopherol and γ-Tocopherol in Preeclampsia and Normal Pregnancy

Antioxidant Function and Health Implications of Vitamin E

Docking of Endothelial Nitric Oxide Synthase (eNOS) to the Mitochondrial Outer Membrane

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