Disease relevance of gamma-Tocopherol

• Gamma-tocopherol: a new player in prostate cancer prevention [1]?
• Subjects in the highest versus lowest quintile of alpha-tocopherol: gamma-tocopherol ratio had an odds ratio of 0.36 (95% confidence interval, 0.14-0.95) for large adenomas [2].
• CONCLUSIONS: This study indicates that both alpha- and gamma-tocopherol decrease platelet aggregation and delay intraarterial thrombus formation, perhaps by an increase in endogenous antioxidant activity [3].
• The reaction of gamma-tocopherol with NO2 to form NO occurs independently of light, whereas alpha-tocopherol requires light to generate NO from NO2. gamma-Tocopherol and aminoguanidine, an NO synthase inhibitor, were superior to alpha-tocopherol in preventing RINm5F cell toxicity induced by Interleukin-1 beta (IL-1 beta) [4].
• Evidence for the nitration of gamma-tocopherol in vivo: 5-nitro-gamma-tocopherol is elevated in the plasma of subjects with coronary heart disease [5].

High impact information on gamma-Tocopherol

• CONCLUSIONS: The use of combined alpha- and gamma- tocopherol supplements should be considered in upcoming prostate cancer prevention trials, given the observed interaction between alpha-tocopherol, gamma-tocopherol, and selenium [6].
• Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer [6].
• Increasing evidence suggests that the different chemical (e.g., alpha- and gamma-tocopherol) and stereochemical (e.g., RRR- and all-racemic-alpha-tocopherol) forms of vitamin E have distinct biologic potencies, pharmacokinetics, and different abilities to prevent neoplastic transformation [7].
• This gene was identified by map-based cloning of the Arabidopsis mutation vitamin E pathway gene3-1 (vte3-1), which causes increased accumulation of delta-tocopherol and decreased gamma-tocopherol in the seed [8].
• Fine-mapping has narrowed QVE7 (a gamma-tocopherol quantitative trait loci) to an 8.5-kb interval encompassing two genes [9].

Chemical compound and disease context of gamma-Tocopherol

• Thus, the ability of gamma-tocopherol to inhibit COX-2 activity independently of its antioxidant function raises important questions regarding potential roles that this form of vitamin E plays in photo-protection and skin cancer chemoprevention [10].
• Radiographic knee osteoarthritis was inversely associated with serum alpha-tocopherol in African Americans and men, positively associated with serum gamma-tocopherol in men, and unassociated with serum delta-tocopherol [11].
• It is known that gamma-tocopherol inhibits human prostate cancer cell proliferation via down-regulation of cyclin-related signalling but tocopherol and tocotrienol metabolites with a shortened phytyl chain, carboxyethyl hydroxychromans, were not previously investigated as anti-proliferative agents [12].
• These results suggest that alpha-tocotrienol and gamma-tocopherol are potent and effective agents for preventing cerebral infarction induced by MCA occlusion [13].
• The effect of gamma-tocopherol on proliferation, integrin expression, adhesion, and migration of human glioma cells [14].

Biological context of gamma-Tocopherol

• Both alpha- and gamma-tocopherol decreased arterial superoxide anion generation, lipid peroxidation and LDL oxidation (all p < 0.05 vs. control), and increased endogenous SOD activity (p < 0.05) [3].
• Differential effects of alpha- and gamma-tocopherol on low-density lipoprotein oxidation, superoxide activity, platelet aggregation and arterial thrombogenesis [3].
• We review current information on the bioavailability, metabolism, chemistry, and nonantioxidant activities of gamma-tocopherol and epidemiologic data concerning the relation between gamma-tocopherol and cardiovascular disease and cancer [15].
• To understand the kinetics and mechanism of alpha-TOH and gamma-tocopherol (gamma-TOH) oxidation in low-density lipoprotein (LDL) (direct vs. radical), we exposed LDL to ONOO- added as a bolus or an infusion [16].
• Supplementation with mixed tocopherols increases serum and blood cell gamma-tocopherol but does not alter biomarkers of platelet activation in subjects with type 2 diabetes [17].

Anatomical context of gamma-Tocopherol

• Plastid enzymes of terpenoid biosynthesis. Purification and characterization of gamma-tocopherol methyltransferase from Capsicum chromoplasts [18].
• All key intermediates of gamma-tocopherol metabolism via this pathway were identified in hepatocyte cultures using gas chromatography-mass spectrometry [19].
• gamma-Tocopherol methyltransferase was solubilized and purified from Capsicum chromoplast membranes by a combination of standard fractionation techniques [18].
• CONCLUSIONS: Plasma and adipose tissue concentrations of gamma-tocopherol are equally good biomarkers of intake [20].
• We used HPLC with electrochemical detection to measure alpha- and gamma-tocopherol in serum, erythrocytes, and platelets, and gas chromatography-mass spectrometry to measure F2-isoprostanes and tocopherol metabolites in urine as markers of oxidative stress and tocopherol intake, respectively [21].

Associations of gamma-Tocopherol with other chemical compounds

• Co-incubation with cholesterol, gamma-tocopherol, or lutein significantly impaired alpha-tocopherol absorption [22].
• Advances in the area of vitamin E metabolism have shown that alpha-CEHC (2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman) and gamma-CEHC (2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman) are formed by a cytochrome p450-mediated process, important for alpha and gamma-tocopherol excretion [23].
• OBJECTIVE: We compared the effects of supplementation with alpha-tocopherol (500 mg) and a gamma-tocopherol-rich compound (500 mg, containing 60% gamma-tocopherol) on serum and cellular tocopherol concentrations, urinary tocopherol metabolite excretion, and in vivo platelet activation in subjects with type 2 diabetes [17].
• RESULTS: After adjustment for dietary antioxidant intakes and other covariates, smokers and passive smokers had significantly lower plasma beta-carotene concentrations than did nonsmokers (0.15, 0.17, and 0.24 micro mol/L, respectively) and significantly higher gamma-tocopherol concentrations (7.8, 7.8, and 6.5 micro mol/L, respectively) [24].
• Plasma concentrations of alpha- and gamma-tocopherol, carotenoids, and retinol were measured with HPLC and plasma vitamin C was measured with a spectrophotometric method in 109 white and African American hemodialysis patients [25].
• Knockdown of gamma-TMT resulted in an up to 95% reduction of alpha-tocopherol in leaves of the transgenics, which was almost quantitatively compensated for by an increase in gamma-tocopherol [26].
• The odds ratio (95% CI) for micromol/l increase in serum concentration of the first-year sample was 0.97 (0.92-1.03) for alpha-tocopherol and 1.10 (0.70-1.74) for gamma-tocopherol [27].

Gene context of gamma-Tocopherol

• Overexpression of VTE1 resulted in an increase in total tocopherol of at least 7-fold in leaves, and a dramatic shift from alpha-tocopherol to gamma-tocopherol [28].
• The biphasic effect on the LDL receptor was specific for alpha-tocopherol in that delta and gamma-tocopherol suppressed LDL receptor binding activity, protein and mRNA at all concentrations tested despite the cells incorporating similar amounts of the three homologues [29].
• In seeds, HPT1 overexpression resulted in a 4-fold increase in HPT specific activity and a total seed tocopherol content that was 40% higher than wild type, primarily because of an increase in gamma-tocopherol content [30].
• Additionally, we demonstrate that afamin has multiple binding sites for both alpha- and gamma-tocopherol [31].
• Interestingly, gamma-tocopherol, which is a homologue of alpha-tocopherol with a comparable antioxidative capacity, showed only a weak suppression of SR activity, SR-A expression and AP-1 activity [32].

Analytical, diagnostic and therapeutic context of gamma-Tocopherol

• This latter property suggests the superiority of gamma-tocopherol in a mammalian biological assay and a role for endogenous NO production in promotion of neoplastic transformation [33].
• Concentrations of alpha-tocopherol and gamma-tocopherol were measured by using HPLC with ultraviolet-visible wavelength detection [34].
• Comparison of plasma alpha and gamma tocopherol levels following chronic oral administration of either all-rac-alpha-tocopheryl acetate or RRR-alpha-tocopheryl acetate in normal adult male subjects [35].
• Alpha-tocopherol and gamma-tocopherol were monitored in human adipose by using needle biopsies in four subjects during a 1-y supplementation trial with 800 mg all-rac-alpha-tocopherol/d, and for 1 additional year after cessation of supplement [36].
• Gas chromatography mass spectrometry analysis of carboxyethyl-hydroxychroman metabolites of alpha- and gamma-tocopherol in human plasma [37].

References