Disease relevance of gamma-Tocopherol

• Failure of high-dose tocopherol to prevent alopecia induced by doxorubicin [1].
• Lack of tocopherol in peripheral nerves of vitamin E-deficient patients with peripheral neuropathy [2].
• These results suggest that adriamycin has at least two mechanisms of tissue damage: one, which involves lipid peroxidation, is blocked by tocopherol and results in cardiac toxicity; the other, which involves binding to DNA, is not antagonized by tocopherol and is responsible for tumor response [3].
• Comparing alpha tocopherol-supplemented subjects with non-alpha tocopherol-supplemented subjects showed a relative risk (RR) of angina pectoris incidence of 0.91 (95% confidence interval[CI], 0.83 to 0.99; P=.04) [4].
• Although no significant associations were observed with beta-carotene, lycopene, or tocopherol, the data suggested an inverse relationship between serum retinol and risk of prostate cancer [5].

Psychiatry related information on gamma-Tocopherol

• To avoid influences of other factors (especially changes in dietary habits) the investigation was performed giving the patients tocopherol and placebo randomly, double blind and cross-over [6].
• After adjusting for other health and life-style factors, we did not observe a statistically significant association between dietary tocopherols and colon cancer [7].
• Evidence of the use of tocopherol as a protective measure or as therapy in neurological diseases other than Alzheimer's disease is less compelling [8].
• It is important to determine if a low level of tocopherols and carotenoids at birth is a normal stage of human development or indicative of deficiency [9].
• DISCUSSION: The deficient concentration of erythrocyte tocopherol together with the altered antioxidant enzyme activities suggest a certain degree of oxidative damage in anorexia nervosa owing to both factors deficient micronutrient intake and oxidative stress [10].

High impact information on gamma-Tocopherol

• Tocopherols and the etiology of colon cancer [11].
• We suggest that these patients are lacking or have a defective liver "tocopherol binding protein" that incorporates alpha-tocopherol into nascent VLDL [12].
• In patients with lipoprotein lipase deficiency, more than 85% of both the circulating triglyceride and tocopherol is contained in the chylomicron fraction [13].
• Addition of both lipase and its activator, apolipoprotein CII, resulted in a further increase in the cellular tocopherol content, but apolipoprotein CII alone had no effect [13].
• Thus, in vitro tocopherol is transferred to cells during hydrolysis of triglyceride by the action of lipase, and for this transfer of tocopherol to occur, the lipase itself must bind to the cell membrane [13].

Chemical compound and disease context of gamma-Tocopherol

• The pathway and enzymes for tocopherol synthesis are homologous in cyanobacteria and plants except for 2-methyl-6-phytyl-1,4-benzoquinone/2-methyl-6-solanyl-1,4-benzoquinone methyltransferase (MPBQ/MSBQ MT), which catalyzes a key methylation step in both tocopherol and plastoquinone (PQ) synthesis [14].
• Evidence relating other carotenoids, tocopherols, and retinol to prostate cancer risk has been equivocal [15].
• Randomized, placebo-controlled trial of combined pentoxifylline and tocopherol for regression of superficial radiation-induced fibrosis [16].
• Adipocyte cholesterol and tocopherol content did not change significantly during weight reduction [17].
• Adipocyte triglyceride, cholesterol, and tocopherol contents were examined in three human obese subjects, all over 150% of ideal weight, who were placed on weight reduction formula diets for 11, 21, and 25 wk, respectively [17].

Biological context of gamma-Tocopherol

• On the other hand, cultivation of target cells with supplemental tocopherol protected them from the toxic effects of the enzymatic oxidant-producing system, indicating a role for membrane-associated free radicals in the mechanism of sister chromatid exchange induction [18].
• To test whether tocopherols (vitamin E) are essential in the protection against oxidative stress in plants, a series of Arabidopsis thaliana vitamin E (vte) biosynthetic mutants that accumulate different types and levels of tocopherols and pathway intermediates were analyzed under abiotic stress [19].
• The vte mutant phenotypes also explain the strong selection for retention of tocopherol biosynthesis during the evolution of seed-bearing plants [20].
• These results confirm that At-VTE3 protein catalyzes the methylation of 2-methyl-6-phytylbenzoquinol in planta and show the utility of this gene in altering soybean tocopherol composition [21].
• Complementation of the mutation with the wild-type transgene largely restored the wild-type tocopherol phenotype [22].

Anatomical context of gamma-Tocopherol

• Levels of tocopherol in adipose tissue were significantly correlated (P less than 0.001) with levels in peripheral nerves [2].
• The addition of lipase to this system also resulted in the transfer of tocopherol (gamma) to the fibroblasts [13].
• The permanent structural coupling between plastoglobules and thylakoid membranes suggests that the lipid molecules contained in the plastoglobule cores (carotenoids, plastoquinone, and tocopherol [vitamin E]) are in a dynamic equilibrium with those located in the thylakoid membranes [23].
• Interestingly, the corresponding maize mutation, sxd1, causes plasmodesmata malfunction, suggesting a link between tocopherol cyclase and plasmodesmata function [24].
• Lymphocytes from patients with CLL had lower values of tocopherol (1.7 +/- 1.0 micrograms/10(9) cells) than lymphocytes from normal subjects (3.8 +/- 0.7 micrograms/10(9) cells) [25].

Associations of gamma-Tocopherol with other chemical compounds

• We report the identification and biotechnological utility of a plant gene encoding the tocopherol (vitamin E) biosynthetic enzyme 2-methyl-6-phytylbenzoquinol methyltransferase [21].
• Intriguingly, the only prokaryotic genomes that contain VTE3-like sequences are those of two species of archea, suggesting that, in contrast to all other enzymes of the plant tocopherol pathway, the evolutionary origin of VTE3 may have been archeal rather than cyanobacterial [14].
• Antioxidant defenses against this damage include ascorbate, tocopherol, and carotenoids [26].
• In the vitamin E group, alpha-tocopherol is generally considered to be the most potent antioxidant with the highest vitamin bioactivity, yet gamma-tocopherol is produced in greater amounts by many plants and is the principal tocopherol in the United States diet [27].
• In all photosynthetic organisms, the carotenoids beta-carotene and zeaxanthin, and tocopherols serve an important photoprotective role, either by dissipating excess excitation energy as heat or by scavenging reactive oxygen species (ROS) and suppressing lipid peroxidation [28].

Gene context of gamma-Tocopherol

• Expression of VTE1 in Escherichia coli resulted in the production of a protein with high tocopherol cyclase and tocotrienol cyclase activity [29].
• In the presence of PKC or PP2A inhibitors, the reduction of PKB phosphorylation by tocopherols was still observed, thus excluding the direct involvement of these enzymes [30].
• Thus, the tocopherols interfere with PKB phosphorylation and reduce proliferation of HMC-1 cells, possibly by modulating either phosphatidylinositol 3-kinase, a kinase phosphorylating PKB (PDK1/2), or a phosphatase that dephosphorylates it [30].
• To investigate whether HPT activity is limiting for tocopherol synthesis in plants, the gene encoding Arabidopsis HPT, HPT1, was constitutively overexpressed in Arabidopsis [31].
• We describe the cloning and expression of two novel genes highly similar to the tocopherol-associated protein (hTAP/SEC14L2/SPF) [32].

Analytical, diagnostic and therapeutic context of gamma-Tocopherol

• Using three-dimensional tomography combined with immunolabeling techniques, we show that the plastoglobules contain the enzyme tocopherol cyclase (VTE1) and that this enzyme extends across the surface monolayer into the interior of the plastoglobules [23].
• Plasma alpha- and beta-carotene, retinol and tocopherol, together with liver tocopherol, from both nonmalignant portions and malignant nodules of the same organ, were determined by high-performance liquid chromatography following a well-assessed technique [33].
• Oxidative stress in fatty livers of obese Zucker rats: rapid amelioration and improved tolerance to warm ischemia with tocopherol [34].
• This defect of the endothelium-dependent vasodilatation was prevented by perfusion of the hearts with superoxide dismutase and pretreatment of the diabetic rats with tocopherol-acetate [35].
• Novel HPLC analysis of tocopherols, tocotrienols, and cholesterol in tissue [36].

References