Regeneration of vitamin E in human platelets

Chan, Alvin C.; Tran, Khai; Raynor, Tina; Gänz, Peter; Chow, Ching K.

doi:10.1016/0891-5849(90)90206-x

Cited by 34 publications

(39 citation statements)

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“…In vitro experiments showed that the tocopherol mediated protection against lipid peroxidation is strongly enhanced by the presence of ascorbate and glutathione (Leung et al, 1981;Niki et al, 1984;Liebler et al, 1986;Wefers and Sies, 1988). Furthermore, ascorbate and glutathione were found to act in concert to keep tocopherol in the reduced, active state in membranes isolated from human platelets and erythrocytes (Chan et al, 1991;Constantinescu et al, 1993). Presumably, the absence of one or more of these three antioxidants in the single and double mutants leads to an increase in oxidative stress in the plant cell, and as a consequence, the amounts of the remaining antioxidants increase.…”

Section: Discussionmentioning

confidence: 99%

Alterations in Tocopherol Cyclase Activity in Transgenic and Mutant Plants of Arabidopsis Affect Tocopherol Content, Tocopherol Composition, and Oxidative Stress

et al. 2005

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Tocopherol belongs to the Vitamin E class of lipid soluble antioxidants that are essential for human nutrition. In plants, tocopherol is synthesized in plastids where it protects membranes from oxidative degradation by reactive oxygen species. Tocopherol cyclase (VTE1) catalyzes the penultimate step of tocopherol synthesis, and an Arabidopsis (Arabidopsis thaliana) mutant deficient in VTE1 (vte1) is totally devoid of tocopherol. Overexpression of VTE1 resulted in an increase in total tocopherol of at least 7-fold in leaves, and a dramatic shift from a-tocopherol to g-tocopherol. Expression studies demonstrated that indeed VTE1 is a major limiting factor of tocopherol synthesis in leaves. Tocopherol deficiency in vte1 resulted in the increase in ascorbate and glutathione, whereas accumulation of tocopherol in VTE1 overexpressing plants led to a decrease in ascorbate and glutathione. Deficiency in one antioxidant in vte1, vtc1 (ascorbate deficient), or cad2 (glutathione deficient) led to increased oxidative stress and to the concomitant increase in alternative antioxidants. Double mutants of vte1 were generated with vtc1 and cad2. Whereas growth, chlorophyll content, and photosynthetic quantum yield were very similar to wild type in vte1, vtc1, cad2, or vte1vtc1, they were reduced in vte1cad2, indicating that the simultaneous loss of tocopherol and glutathione results in moderate oxidative stress that affects the stability and the efficiency of the photosynthetic apparatus.Vitamin E encompasses a class of lipid antioxidants consisting of four forms each of tocopherol and tocotrienol. Because of its high economical value and importance for human nutrition, much effort has been invested to elucidate the tocopherol biosynthetic pathway in plants and Cyanobacteria and to identify limiting steps by overexpression of candidate genes in transgenic plants. The hydroquinone ring of tocopherol is derived from the shikimate pathway of aromatic amino acid synthesis. Homogentisate, the precursor for the synthesis of tocopherol, tocotrienol, and plastoquinone, is synthesized by p-hydroxyphenylpyruvate dioxygenase (HPPD; Fig. 1; Norris et al., 1998) (Collakova et al., 2003a). Final methylation by g-tocopherol methyltransferase (g-TMT, VTE4) results in the production of a-tocopherol. a-Tocopherol is the predominant form in leaves, whereas g-tocopherol is most abundant in seeds of Arabidopsis (Shintani and DellaPenna, 1998). Side reactions of VTE1, VTE3, and VTE4 result in the production of minor tocopherol forms in Arabidopsis seeds or leaves (d-tocopherol, b-tocopherol; Fig. 1).Under oxidative stress, the amounts of different antioxidants strongly increase in plants, and it is believed that this results in an increased capacity to scavenge reactive oxygen species (Noctor and Foyer, 1998;Collakova et al., 2003b). The accumulation of antioxidants under stress is at least in part mediated by induction of gene expression. For example, HPPD and HPT1, two steps of tocopherol synthesis, were shown to be induced under light stress (Coll...

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Section: Discussionmentioning

confidence: 99%

Alterations in Tocopherol Cyclase Activity in Transgenic and Mutant Plants of Arabidopsis Affect Tocopherol Content, Tocopherol Composition, and Oxidative Stress

et al. 2005

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“…This synergistic effect between these two functionally similar antioxidants provides further supporting evidence that the intracellular antioxidant defense machinery is organized as a network and functions as an integrated system. It is generally accepted that GSH, ascorbic acid, and ␣-tocopherol operate as a reaction chain to ensure maximum membrane protection against oxidative damage (Chan et al, 1991). GSH, either exogenously supplied or endogenously regenerated from oxidized glutathione by glutathione reductase, is one of the most important reducing agents in the regeneration of ascorbic acid from its oxidized form, dehydroascorbate.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Glutathione Cardioprotection by Ascorbic Acid in Myocardial Reperfusion Injury

Gao¹,

Chenlin²,

Gao³

et al. 2002

J Pharmacol Exp Ther

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The present experiment determined the effects of glutathione and ascorbic acid, the two most important hydrophilic antioxidants, on myocardial ischemia-reperfusion injury and evaluated their relative therapeutic values. Isolated rat hearts were subjected to ischemia (30 min) and reperfusion (120 min) and treated with ascorbic acid, glutathione monoethyl ester (GSHme), or their combination at the onset of reperfusion.

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“…On the contrary, a decrease in the parameters measured was observed which is highly suggestive of an antioxidant effect of the supplementation. Vitamin C has been reported in human studies both to decrease platelet aggregation in vivo (Cordova et al, 1982) and to regenerate vitamin E in platelets (Chan et al, 1991) which might in turn be expected to reduce platelet aggregation (Steiner, 1978) as was recently shown by Calzada et al (1997). In a double-blind, placebo-controlled human trial (Calzada et al, 1997) vitamin C supplementation (250 mgad for 8 wk) by itself had no signi®cant effect on platelet function, although a tendency towards decreased platelet aggregability and an increased sensitivity to PGE 1 inhibition was observed.…”

Section: Discussionmentioning

confidence: 99%

Do iron and vitamin C co-supplementation influence platelet function or LDL oxidizability in healthy volunteers?

Yang

Kelly

et al. 1999

Eur J Clin Nutr

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Objective: To examine the effect of co-supplementation with iron and vitamin C on antioxidant status, platelet function and low density lipoprotein oxidation in normal healthy volunteers. Design: The study was carried out with two groups of 20 subjects each acting as their own control, comparing presupplemention with postsupplemention. One group was supplemented with iron and the RDA level of vitamin C and the second group with iron and 260 mgad vitamin C. Setting: The International Antioxidant Research Centre, The Guy's, King's College and St Thomas's School of Biomedical Science, Guy's Campus, London. Subjects: Forty normal healthy volunteers, recruited from the staff of the Medical School and Hospital in which two volunteers withdrew during the study. Interventions: Subjects in both studies were randomly assigned to one of two groups (5 males and 5 females group) and received supplements containing iron (14 mgad) and either 60 mgad (Group A) or 260 mgad (Group B) vitamin C for 12 wk. Blood samples were taken at 6 wk and 12 wk, and prior to supplementation and analysed for iron and antioxidant status (transferrin bound iron, vitamin C and E, and b-carotene levels) in both studies. Samples from the ®rst study were analysed for the susceptibility of LDL isolated from plasma to Cu 2 -induced oxidation and samples from the second for platelet function. Results: Transferrin-bound iron was signi®cantly increased (P`0.05) at 12 wk, in Group A subjects (from 14.9 AE 5.3 mmolal to 19.5 AE 2.3 mmolal; mean AE s.d.; n 19), whereas those in Group B showed a signi®cant increase (P`0.05) after 6 wk (from 15.8 AE 4.5 mmolal to 20.4 AE 6.6 mmolal; n 19) which decreased at 12 wk (16.3 AE 5.0 mmolal). Plasma total ascorbate signi®cantly increased from an initial level of 59.3 AE 21.3 mmolal to 87.6 AE 29.0 mmolal after 6 wk and 81.7 AE 11.4 mmolal after 12 wk following the Group B supplementation, but only after 12 wk in Group A (from 64.0 AE 24.8 mmolal to 77.2 AE 13.2 mmolal). Plasma a-tocopherol concentrations were signi®cantly increased after 6 wk and 12 wk with both levels of supplementation (from 24.2 AE 5.7 mmolal Group A and 23.4 AE 5.3 mmolal Group B to 26.3 AE 5.5 mmolal and 25.7 AE 4.7 mmolal respectively at 12 wk). The mean lag phase to oxidation of low density lipoprotein (LDL) was signi®cantly increased in subjects in Group B after 12 wk ingestion of iron and 260 mg vitamin C (from 80.0 AE 14.8 min to 97.2 AE 16.9 min; n 9). Platelet sensitivity to ADP-induced aggregation was signi®cantly decreased (P`0.05) by 12 wk in Group A (from EC 50 2.3 AE 1.3 mM to 3.7 AE 2.2 mM; n 10), whereas those receiving higher vitamin C showed a signi®cant decrease (P`0.05; from EC 50 1.9 AE 0.6 mM to 3.1 AE 1.8 mM) after 6 wk which subsequently increased towards presupplemental levels (2.6 AE 1.6 mM). Platelets from the latter subjects showed a signi®cant reduction in ADP-induced ATP secretion at both 6 wk and 12 wk. Conclusion: The results show modest bene®cial effects on LDL oxidation and platelet function following supplementatio...

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Regeneration of vitamin E in human platelets

Cited by 34 publications

References 0 publications

Alterations in Tocopherol Cyclase Activity in Transgenic and Mutant Plants of Arabidopsis Affect Tocopherol Content, Tocopherol Composition, and Oxidative Stress

Alterations in Tocopherol Cyclase Activity in Transgenic and Mutant Plants of Arabidopsis Affect Tocopherol Content, Tocopherol Composition, and Oxidative Stress

Enhancement of Glutathione Cardioprotection by Ascorbic Acid in Myocardial Reperfusion Injury

Do iron and vitamin C co-supplementation influence platelet function or LDL oxidizability in healthy volunteers?

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