Glutathione biosynthesis in the isolated perfused rat lung: utilization of extracellular glutathione

Berggren, Margareta; Dawson, Janet R.; Moldéus, Peter

doi:10.1016/0014-5793(84)80938-2

Cited by 70 publications

(17 citation statements)

References 19 publications

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“…Effect of GSH and GSH Ester on BSO-Induced Inhibition of Accessory Cell-Independent Proliferation. When purified T cells were treated with BSO there was a marked inhibition of proliferation ( (31,41), bovine arterial endothelial cells (42), and lung (43,44). Although it is possible that the isolated T cells can take up intact GSH, no evidence for this was found in studies on mouse peripheral lymphocytes in vivo (43), human lymphoid cell lines (31,41), and human peripheral lymphocytes (6,11 (45).…”

Section: Resultsmentioning

confidence: 99%

Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens.

Suthanthiran

Anderson

Sharma

et al. 1990

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

335

176

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Regulation of proliferation of normal human T lymphocytes (T cells) by glutathione (GSH) was explored with T-cell activation models that-do not require accessory cell signals. L-Buthionine-(S,R)-sulfoximine (BSO), which inactivates y-glutamylcysteine synthetase and therefore inhibits GSH synthesis, inhibited proliferation elicited by monoclonal antibodies directed at cluster designation 2 (CD2) and CD3

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Section: Resultsmentioning

confidence: 99%

Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens.

Suthanthiran

Anderson

Sharma

et al. 1990

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

335

176

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“…The utilization of extracellular GSH seems to involve degradation of GSH, transport of products, and intracellular synthesis of GSH (4,6); studies on human lymphoid cells (32,33), kidney (34), lung (14,35), and bovine pulmonary artery endothelial cells (36) support this. That the tissue GSH levels of BSO-treated mice, which are very low (0.06-0.3 mM), do not increase significantly when the plasma levels of GSH are 5 mM or higher (Table 1) indicates that there is little if any transport of GSH.…”

Section: Discussionmentioning

confidence: 97%

Glutathione is required for intestinal function.

Mårtensson

Jain²,

Meister³

1990

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

255

167

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Glutathione (GSH) deficiency produced in mice by giving buthionine sulfoximine leads to severe degeneration of the epithelial cells of the jejunum and colon. This is prevented by giving GSH monoester (orally or i.p.) and also by giving GSH (orally, but not i.p.). The i.p. administration leads to high plasma levels of GSH but does not appreciably increase GSH levels in intestinal mucosa or pancreas. These and previous studies on lens, lung, lymphocytes, liver, heart, and skeletal muscle indicate that there is very little, if any, transport of intact GSH from plasma to these tissues. Cells can use extracellular GSH by a pathway involving its cleavage, uptake of products and intracellular GSH synthesis. Epithelial cells of the gastrointestinal tract may use this pathway and can also take up lumenal GSH (which arises partly from the bile) by a mechanism(s) that may involve transport of dipeptides or of GSH. It is suggested that biliary GSH normally functions in the protection of intestinal mucosa. Administration of GSH may be protective of the gastrointestinal epithelium and may also serve as a good source of cysteine moieties for intracellular GSH synthesis in the gastrointestinal tract and in other tissues. Administration of GSH delivery agents such as GSH esters is more effective than administration of GSH in increasing cellular and mitochondrial levels of GSH.Administration to experimental animals of L-buthionine-SR-sulfoximine (BSO), a transition-state inhibitor of yglutamylcysteine synthetase, leads to decreased synthesis of glutathione (GSH) in many tissues (1-4). Decreased cellular GSH levels and capacity for GSH synthesis sensitize cells to radiation and to certain drugs; these effects provide a potentially useful approach in cancer therapy (5-12). Administration of BSO offers several advantages over other methods of cellular GSH depletion, one of which is that it makes possible the selective decrease of cellular GSH for relatively long periods, thus facilitating study of the effects of GSH deficiency on cell structure and function. Administration of BSO to mice for 9-21 days, without application of stress, led to marked structural changes in skeletal muscle (13), lung (14), and epithelial cells ofnewborn lens (15); such effects were not found in heart (13) and liver (14). Mitochondrial damage is found in tissues affected by ; the mitochondrial levels of GSH in tissues markedly affected by GSH depletion (lung, muscle, lens) were -20%o of the untreated controls, whereas in heart and liver the mitochondrial GSH levels were >40% of the controls. Mitochondrial and other cellular damage was prevented by simultaneous administration of GSH monoester but not by administration of GSH. GSH monoesters can enter cells effectively and are converted to GSH intracellularly (16)(17)(18)(19). In contrast, GSH is poorly transported into cells.These studies were stimulated by the observation (13) that administration of BSO to 28-to 30-g mice for 9-21 days led to a marked decrease in weight gain and that simultaneous ...

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“…In addition, GSSG has been shown to support GSH synthesis in isolated rat lungs. albeit lcss efliciently than with GSH (15), and in individual patients it is possible that GSSG released from other organs could have been undergoing net uptake by the lungs.…”

Section: Methodsmentioning

confidence: 99%

Oxidant Stress Responses in Premature Infants during Exposure to Hyperoxia

et al. 1993

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ABSTRACT. To assess oxidant stress responses in newborn infants treated with elevated concentrations of oxygen, we measured plasma concentrations of glutathione (GSH) and glutathione disulfide (GSSG) in newborn infants ranging from 23 to 42 wk gestational age. All infants recruited into the study were mechanically ventilated and had catheters placed in their umbilical arteries a s part of their normal clinical management. Blood samples were obtained on d 1,3, and 5 and weekly thereafter or until the catheters were removed. W e observed plasma concentrations of GSSG in these infants that were frequently an order of magnitude higher than the 0.1 to 0.3 pM we find in adults. Interestingly, plasma GSSG concentrations were inversely correlated to the inspired oxygen tensions. This effect appeared to arise from the patient selection criteria whereby, of the infants studied, those breathing the lowest partial pressures of oxygen were the smallest and gestationally youngest. A second observation was that plasma concentrations of G S H in the premature infants were substantially, indeed often dramatically, lower than we have observed in adult humans (6 to 10 pM). Finally, we found that in patients with both umbilical arterial and umbilical venous catheters arterial GSSG concentrations were consistently higher than venous concentrations; conversely, arterial GSI4 concentrations were lower than venous concentrations. The elevated GSSG concentrations we observed in these infants indicate marked oxidant stress responses in prematurely born infants, even in those infants exposed only to room air. The positive arteriovenous gradients of GSSG concentrations across the lungs of these infants suggest that a t least some of the increased plasma GSSG originates in the lung. The low plasma G S H concentrations we observed in these same infants suggest deficiencies in an antioxidant that has been shown in numerous animal studies to be critical for prevention of hyperoxia-induced lung injury. Finally, the negative arteriovenous gradients of G S H concentrations across the lung provide the first evidence in humans for pulmonary uptake of GSH. (Pediatr Res 34: 360-365,1993) Abbreviations Fi02, fraction inspired oxygen GGT, y-glutamyltranspeptidase GSH, glutathione GSSG, glutathione disulfide PAO~, alveolar oxygen tension Pao2, arterial oxygen tension

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Glutathione biosynthesis in the isolated perfused rat lung: utilization of extracellular glutathione

Cited by 70 publications

References 19 publications

Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens.

Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens.

Glutathione is required for intestinal function.

Oxidant Stress Responses in Premature Infants during Exposure to Hyperoxia

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