Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042875 (vitamin E deficiency)
 916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From the severe neurological syndromes resulting from vitamin E deficiency, it is evident that an adequate supply of the brain with alpha-tocopherol (alphaTocH), the biologically most active member of the vitamin E family, is of utmost importance. However, uptake mechanisms of alphaTocH in cells constituting the blood-brain barrier are obscure. Therefore, we studied the interaction of low (LDL) and high (HDL) density lipoproteins (the major carriers of alphaTocH in the circulation) with monolayers of primary porcine brain capillary endothelial cells (pBCECs) and compared the ability of these two lipoprotein classes to transfer lipoprotein-associated alphaTocH to pBCECs. With regard to potential binding proteins, we could identify the presence of the LDL receptor and a putative HDL3 binding protein with an apparent molecular mass of 100 kDa. At 4 degrees C, pBCECs bound LDL with high affinity (K(D) = 6 nM) and apolipoprotein E-free HDL3 with low affinity (98 nM). The binding capacity was 20,000 (LDL) and 200,000 (HDL3) lipoprotein particles per cell. alphaTocH uptake was approximately threefold higher from HDL3 than from LDL when [14C]alphaTocH-labeled lipoprotein preparations were used. The majority of HDL3-associated alphaTocH was taken up in a lipoprotein particle-independent manner, exceeding HDL3 holoparticle uptake 8- to 20-fold. This uptake route is less important for LDL-associated alphaTocH (alphaTocH uptake approximately 1.5-fold higher than holoparticle uptake). In line with tracer experiments, mass transfer studies with unlabeled lipoproteins revealed that alphaTocH uptake from HDL3 was almost fivefold more efficient than from LDL. Biodiscrimination studies indicated that uptake efficacy for the eight different stereoisomers of synthetic alphaTocH is nearly identical. Our findings indicate that HDL could play a major role in supplying the central nervous system with alphaTocH in vivo.
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PMID:Uptake of lipoprotein-associated alpha-tocopherol by primary porcine brain capillary endothelial cells. 1073 92

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 alpha-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.
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PMID:Increased atherosclerosis in hyperlipidemic mice deficient in alpha -tocopherol transfer protein and vitamin E. 1109 17

Vitamin E has failed to protect humans from cardiovascular disease outcome, yet its role in experimental atherosclerosis remains less clear. A previous study (Proc. Natl. Acad. Sci. USA 97:13830-13834; 2000) showed that vitamin E deficiency caused by disruption of the alpha-tocopherol transfer protein gene (Ttpa) is associated with a modest increase in atherosclerosis in apolipoprotein E gene deficient (Apoe(-/-)) mice. Here we confirm this finding and report that in Apoe(-/-)Ttpa(-/-) mice dietary alpha-tocopherol (alphaT) supplements restored circulating and aortic levels of alphaT, and decreased atherosclerosis in the aortic root to a level comparable to that seen in Apoe(-/-) mice. However, such dietary supplements did not decrease disease in Apoe(-/-) mice, whereas dietary supplements with a synthetic vitamin E analog (BO-653), either alone or in combination with alphaT, decreased atherosclerosis in Apoe(-/-) and in Apoe(-/-)Ttpa(-/-) mice. Differences in atherosclerosis were not associated with changes in the arterial concentrations of F(2)-isoprostanes and cholesterylester hydro(pero)xides, nor were they reflected in the resistance of plasma lipids to ex vivo oxidation. These results show that vitamin E at best has a modest effect on experimental atherosclerosis in hyperlipidemic mice, and only in situations of severe vitamin E deficiency and independent of lipid oxidation in the vessel wall.
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PMID:Protective effect of vitamin E supplements on experimental atherosclerosis is modest and depends on preexisting vitamin E deficiency. 1689 92

Abnormal function of apolipoprotein E (apoE) has been implicated in the incidence of some neurological disorders including dementia. Our recent experiments have shown that apoE deficiency alters the dynamics of alpha tocopherol (vitamin E) handling by brain. In the current investigation, we examined the uptake and retention of tritium-labeled alpha tocopherol that was injected into the lateral cerebral ventricles of apoE-deficient and wild type mice that were fed vitamin E-deficient diet. Eighteen weeks-old, male mice were fed vitamin E-deficient diets for 28 weeks. Labeled cholesterol was injected with the radioactive tocopherol and the cholesterol counts were used as internal standard. After an equilibration time of 48 h, radioactive alpha tocopherol levels in most brain regions were higher in apoE deficient animals when compared with the wild type. Along with our other data, this suggests that the clearance of vitamin E is slower in apoE-deficient brains. Nearly all of the injected alpha tocopherol was unchanged in the brains of both apoE-deficient and wild type animals (even with the additional dietary stress of vitamin E deficiency) suggesting low turnover rate of tocopherol in brain. The data strongly suggest that apoE is a key protein involved with the transport and/or retention of alpha tocopherol in brain.
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PMID:Brains of apolipoprotein E deficient mice fed vitamin E deficient diets show alteration in handling alpha tocopherol injected into the cerebral ventricles. 1944