On the Existence of a Hitherto Unrecognized Dietary Factor Essential for Reproduction

Evans, Herbert M.; Bishop, Katharine S.

doi:10.1126/science.56.1458.650

Cited by 870 publications

(415 citation statements)

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“…This fertility defect presumably resulted from vitamin E deficiency. Vitamin E is required to prevent fetal resorption in rodents (32,33), and vitamin E supplementation (1,000 units͞kg of diet) completely reversed the fertility defect (not shown). Ttpa Ϫ/Ϫ males had no obvious impairment in fertility.…”

Section: Resultsmentioning

confidence: 99%

Increased atherosclerosis in hyperlipidemic mice deficient in α-tocopherol transfer protein and vitamin E

Terasawa

Ladha

Leonard

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

224

156

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Although lipid peroxidation in the subendothelial space has been hypothesized to play a central role in atherogenesis, the role of vitamin E in preventing lipid peroxidation and lesion development remains uncertain. Here we show that in atherosclerosis-susceptible apolipoprotein E knockout mice, vitamin E deficiency caused by disruption of the ␣-tocopherol transfer protein gene (Ttpa) increased the severity of atherosclerotic lesions in the proximal aorta. The increase was associated with increased levels of isoprostanes, a marker of lipid peroxidation, in aortic tissue. These results show that vitamin E deficiency promotes atherosclerosis in a susceptible setting and support the hypothesis that lipid peroxidation contributes to lesion development. Ttpa ؊/؊ mice are a genetic model of vitamin E deficiency and should be valuable for studying other diseases in which oxidative stress is thought to play a role.antioxidants O xidative modification of lipoproteins (e.g., low-density lipoproteins) has been hypothesized to play a key role in the pathogenesis of atherosclerosis (1, 2). Because vitamin E is the most potent lipid-soluble antioxidant normally found on lipoproteins in the plasma, there is strong interest in the relationship between vitamin E levels and the development of atherosclerosis. In animal models and human clinical trials, studies of the effects of vitamin E supplementation on atherosclerosis have yielded conf licting results (3-8), and little is known about the effects of vitamin E deficiency on atherosclerosis development (9).The major form of vitamin E in human plasma and tissues is ␣-tocopherol (10). ␣-Tocopherol enrichment of plasma and tissues is mediated by the ␣-tocopherol transfer protein (␣-TTP), a cytosolic lipid-transfer protein expressed in the liver (11)(12)(13)(14). Although the mechanism is unknown (15), ␣-TTP is believed to selectively transfer ␣-tocopherol from lipoproteins taken up by hepatocytes via the endocytic pathway to newly secreted lipoproteins, which facilitate its delivery to peripheral tissues (12). Humans with ␣-TTP gene defects have extremely low plasma ␣-tocopherol concentrations and develop severe neurodegenerative disease unless they are treated with high doses of vitamin E (16-18).To investigate the relationship between vitamin E deficiency and atherosclerosis, we used gene targeting to disrupt the mouse ␣-TTP gene (Ttpa) and generate a genetic model of vitamin E deficiency. We then crossed the ␣-TTP-deficient mice (Ttpa Ϫ/Ϫ ) mice with apolipoprotein (apo) E knockout (Apoe Ϫ/Ϫ ) mice (19), which spontaneously develop atherosclerosis on a chow diet (20,21). This enabled us to generate Apoe Ϫ/Ϫ mice with different Ttpa genotypes (ϩ͞ϩ, ϩ͞Ϫ, and Ϫ͞Ϫ) to test the hypothesis that ␣-TTP and vitamin E deficiency increase atherosclerosis in a susceptible setting. Materials and MethodsGeneration of ␣-TTP Knockout Mice. A 14-kb 129͞Sv genomic clone containing the Ttpa gene was isolated and subcloned into pBSSKII. A sequence replacement vector was constructed by PCR amplifica...

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Section: Resultsmentioning

confidence: 99%

Increased atherosclerosis in hyperlipidemic mice deficient in α-tocopherol transfer protein and vitamin E

Terasawa

Ladha

Leonard

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

224

156

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“…Initialementidentifiee comme un compose necessaire a la reproduction des rats en 1922 (Evans et Bishop, 1922), les proprietes antioxydantes de la vitamine E furent decrites en 1937. L'activite vitaminique de la vitamine E, definie par la capacite a prevenir la mort des embryons chez des rattes gestantes carencees en vitamine E, est exprimee en tocopherolsequivalent (activite de 1 mg de RRR-atocopherol), ou en unite internationale (la reference est dans ce cas 1 mg de all-raca-tocopherol acetate).…”

Section: Quelques Generalitesunclassified

Vitamine E et physiologie du tissu adipeux

Landrier

2011

OCL

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“…Vitamin E was discovered as a micronutrient that is indispensable for reproduction in female rats (1). In humans, vitamin E deficiency can result in various neurological lesions (2,3).…”

Section: Ietary Antioxidants (Eg Vitamin E (Including ␣-Tocoph-mentioning

confidence: 99%

Inhibition of NF-κB and Oxidative Pathways in Human Dendritic Cells by Antioxidative Vitamins Generates Regulatory T Cells

Tan

Sagoo

Chan

et al. 2005

The Journal of Immunology

198

159

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Dendritic cells (DCs) are central to T cell immunity, and many strategies have been used to manipulate DCs to modify immune responses. We investigated the effects of antioxidants ascorbate (vitamin C) and α-tocopherol (vitamin E) on DC phenotype and function. Vitamins C and E are both antioxidants, and concurrent use results in a nonadditive activity. We have demonstrated that DC treated with these antioxidants are resistant to phenotypic and functional changes following stimulation with proinflammatory cytokines. Following treatment, the levels of intracellular oxygen radical species were reduced, and the protein kinase RNA-regulated, eukaryotic translation initiation factor 2α, NF-κB, protein kinase C, and p38 MAPK pathways could not be activated following inflammatory agent stimulation. We went on to show that allogeneic T cells (including CD4+CD45RO, CD4+CD45RA, and CD4+CD25− subsets) were anergized following exposure to vitamin-treated DCs, and secreted higher levels of Th2 cytokines and IL-10 than cells incubated with control DCs. These anergic T cells act as regulatory T cells in a contact-dependent manner that is not dependent on IL-4, IL-5, IL-10, IL-13, and TGF-β. These data indicate that vitamin C- and E-treated DC might be useful for the induction of tolerance to allo- or autoantigens.

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On the Existence of a Hitherto Unrecognized Dietary Factor Essential for Reproduction

Cited by 870 publications

References 1 publication

Increased atherosclerosis in hyperlipidemic mice deficient in α-tocopherol transfer protein and vitamin E

Increased atherosclerosis in hyperlipidemic mice deficient in α-tocopherol transfer protein and vitamin E

Vitamine E et physiologie du tissu adipeux

Inhibition of NF-κB and Oxidative Pathways in Human Dendritic Cells by Antioxidative Vitamins Generates Regulatory T Cells

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