Uptake and Reduction of Oxidized and Reduced Ascorbate by Human Leukocytes

Bigley, Robert H.; Stanková, L

doi:10.1084/jem.139.5.1084

Cited by 73 publications

(21 citation statements)

References 17 publications

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“…The mechanisms to safeguard the functions of the macrophage include enzymes such as superoxide dismutase and catalase or physiological redox-substances such as glutathione, vitamin E [Baehner et al, 1977] and ascorbate which has been shown to be a scavenger of radicals [Nishikimi, 1975;Bodannes and Chan, 1979], It has been found in vitro that ascorbic acid, cytochrome C and catalase exert a protective influence on rabbit mac rophages from phagocytosis-dependent injuries [McGee and Myrvik, 1979], For these reasons, the ob served strong consumption of ascorbic acid during macrophage phagocytosis may be due to a protective action against autooxidation. The intracellular pool of ascorbic acid can be replenished by uptake of dehydroascorbic acid [Bigley and Stankova, 1974] or ascorbic acid from plasma following phagocytosis [Schmidt and Moser, 1985].…”

Section: Discussionmentioning

confidence: 99%

Effect of Functional Stimulation on Ascorbate Content in Phagocytes under Physiological and Pathological Conditions

Oberritter¹,

Glatthaar²,

Moser³

et al. 1986

Int Arch Allergy Immunol

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Neutrophil polymorphonuclear leucocytes and macrophages contain 10–40 times increased intracellular ascorbate concentrations compared to plasma. A slight decrease of ascorbate content could be observed in total white blood cells and in monocytes upon stimulation with opsonized zymosan. These decreases were more pronounced in peritoneal and alveolar macrophages from rats. In patients with rheumatoid disease whose phagocytes are exposed to a constant challenge, significantly lowered intracellular ascorbate contents were found in neutrophils and mononuclear cells. Surgical and thermal trauma in rats depressed intracellular ascorbate levels in peritoneal macrophages. These results are indicative of an essential role ascorbic acid plays in phagocytic cells.

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Section: Discussionmentioning

confidence: 99%

Effect of Functional Stimulation on Ascorbate Content in Phagocytes under Physiological and Pathological Conditions

Oberritter¹,

Glatthaar²,

Moser³

et al. 1986

Int Arch Allergy Immunol

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“…Methylene blue and sodium ascorbate can alter the intracellular "redox" state (7,8) and sodium ascorbate has been reported to cause contraction of ileal muscle strips (16 For each experiment, artery segments from a single umbilical cord were incubated for 2 hr in the indicated medium in room air. Agonists were added and incubations were terminated after 2 min (serotonin, ionophore A23187, bradykinin, and histamine) or 6 min (sodium ascorbate, methylene blue).…”

Section: Discussionmentioning

confidence: 99%

Oxygen and cyclic nucleotides in human umbilical artery.

Clyman¹,

Blacksin²,

Manganiello³

et al. 1975

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

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In the human umbilical artery 02 has a direct contractile effect and is also required for induction of contraction by several other agents. Agonists that cause contraction (bradykinin, histamine, and serotonin) cause accumulation of guanosine 3':5'-monophosphate (cGMP) without altering adenosine 3':5'-monophosphate (cAMP). They appear to act through two different mechanisms: one Ca++-dependent, the other Ca++-inhibited. 02 increased the cGMP content of the artery in a Ca++-dependent manner without affecting the cAMP content. Inhibitors of oxidative phosphorylation (oligomycin and 2,4-dinitrophenol) did not diminish this effect of 02.02 was required for demonstration of the Ca++-dependent accumulation of cGMP in response to bradykinin, histamine, and ionophore A23187. The effect of the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine on basal cGMP content and on the bradykinin-induced accumulation was also dependent on the presence of 02. Methylene blue and sodium ascorbate caused cGMP accumulation in 02-deprived arteries. Their effects were not diminished in Ca++-depleted arteries and, in fact, seemed to be inhibited when 2.7 mM Ca++ was present in the medium. The effects of these agents and of serotonin on cGMP, which were inhibited by Ca++, were also inhibited by 02. These non Ca++-, non 02-dependent agents (methylene blue, ascorbate, and serotonin) did not, however, permit demonstration of the effects of the Ca++-and Ordependent agonists on Ordeprived arteries. It appears that there are in the umbilical artery (and probably in other tissues also) at least two separate mechanisms for control of cGMP synthesis that are influenced differently by Ca++-and 02-linked processes.There is considerable evidence that in human umbilical artery an increase in 02 tension induces contraction and a decrease leads to relaxation (1-3). Humoral agents that cause contraction of the artery in vitro induce accumulation of guanosine 3':5'-monophosphate (cGMP) and those that initiate relaxation cause accumulation of adenosine 3':5'-monophosphate (cAMP) (4). Regulation of cGMP content appears to be effected through two distinct mechanisms: one that requires Ca and one that is inhibited by Ca++ (5). In the experiments reported here the effects of 02 on cyclic nucleotide metabolism in human umbilical artery were investigated. It was found that 02 caused accumulation of cGMP in a Ca++-dependent manner, without affecting the cAMP content of the artery. Further, agonists that required Ca++ in order to bring about an increase in cGMP content also required 02, whereas the effects of the agonists that were inhibited by Ca++ were also inhibited by 02-METHODS AND MATERIALS Human umbilical cords from full-term deliveries, obtained within 30 min of delivery, were dissected and prepared for incubation as previously described (4). For these procedures Hanks' medium without Ca++ and Mg++ was used at room were randomly assigned to 25 ml Erlenmeyer flasks containing 4 ml of medium as indicated in specific experiments.The complete medi...

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“…Similarly, for ascorbic acid and DHA, there is a potential discrepancy between the dominant substrate found and the dominant substrate transported in vivo (2). Whether ascorbate accumulation is mediated by DHA or ascorbic acid has been a central issue in ascorbate biology for more than 50 years (32,33). Based on the results in the present report, ascorbate analogs offer a novel means to resolve this issue and to test the contribution of each transport mechanism toward tissue accumulation of vitamin C in vivo.…”

Section: -Bromo-6-deoxy-l-ascorbic Acidmentioning

confidence: 99%

6-Bromo-6-deoxy-l-ascorbic Acid

Corpe

Lee

Kwon

et al. 2005

Journal of Biological Chemistry

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Vitamin C intracellular accumulation is mediated by Na؉ -dependent vitamin C transporters SVCT1 and -2 and dehydroascorbic acid transporters GLUT1 and -3. It is unclear which pathways dominate in vivo. As a new step to resolve this issue, we identified and tested 6-bromo-6-deoxy-L-ascorbic acid as a specific candidate for SVCTs. In high performance liquid chromatography and electron paramagnetic resonance analyses, the reduced compounds ascorbic acid and 6-bromo-6-deoxy-L-ascorbic acid were similar. The oxidized products 6-bromo-6-deoxy dehydroascorbic acid (BrDHA) and dehydroascorbic acid (DHA) had comparable stabilities, based on reduction recoveries. Upon expression of GLUT1 or GLUT3 in Xenopus oocytes, BrDHA was neither transported nor bound, in contrast to robust transport of DHA. The findings were not explained by differences in the oocyte reduction of DHA and BrDHA because lysed oocytes reduced both compounds equally. Further, there was no transport of the reduced compound, 6-bromo-6-deoxy-L-ascorbic acid, by GLUT1 or GLUT3. As a prerequisite for investigating 6-bromo-6-deoxy-L-ascorbic acid transported by SVCTs, SVCT2 transport activity in oocytes was enhanced 14-fold by construction and use of a vector that added a fixed poly(A) tail to the 3 end of cRNA. For SVCT1 and SVCT2 expressed in oocytes, similar K m and V max values were observed for ascorbic acid and 6-bromo-6-deoxy-Lascorbic acid. In human fibroblasts, predicted to have SVCT-mediated ascorbate accumulation, K m and V max values were again comparable for ascorbic acid and 6-bromo-6-deoxy-L-ascorbic acid. Using activated human neutrophils, predicted to have ascorbate accumulation mediated predominantly by DHA and GLUT transporters, 6-bromo-6-deoxy-L-ascorbic acid accumulation was <1% of accumulation when compared with ascorbic acid. We conclude that 6-bromo-6-deoxy-L-ascorbic acid is the first transport substrate identified as completely specific for SVCTs, but not GLUTs, and provide a new strategy to determine the contribution of each pathway to ascorbate accumulation.

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Uptake and Reduction of Oxidized and Reduced Ascorbate by Human Leukocytes

Cited by 73 publications

References 17 publications

Effect of Functional Stimulation on Ascorbate Content in Phagocytes under Physiological and Pathological Conditions

Effect of Functional Stimulation on Ascorbate Content in Phagocytes under Physiological and Pathological Conditions

Oxygen and cyclic nucleotides in human umbilical artery.

6-Bromo-6-deoxy-l-ascorbic Acid

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