Skip to main content
SpringerLink
Log in

L-2-Oxothiazolidine-4-carboxylate protects cultured endothelial cells against hyperoxia-induced injury

  • Original Articles
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

When bovine pulmonary artery endothelial monolayers were exposed to hyperoxia (95% O2 and 5% Co2), they responded by selectively elevating the intracellular concentration of glutathione without affecting the activities of glutathione peroxidase or glutathione reductase.l-2-Oxothiazolidine-4-carboxylate, an intracellular cysteine-delivering agent, further enhanced the intracellular concentration of glutathione in oxygen-exposed endothelial cells and protected them from the lethal effect of hyperoxia. In contrast, buthionine sulfoximine, a potent inhibitor ofγ-glutamylcysteine synthetase, reduced the glutathione concentration and rendered the cells more sensitive to the toxic effect of oxygen. Bothl-2-oxothiazolidine-4-carboxylate and buthionine sulfoximine had no effect on the activities of glutathione peroxidase or glutathione reductase. Our results suggest thatl-2-oxothiazolidine-4-carboxylate may have the potential of preventing oxygen toxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Frank, L., andD. Massaro. 1980. Oxygen toxicity.Am. J. Med. 69:117–126.

    Google Scholar 

  2. Kistler, G. S., P. R. B. Caldwell andE. R. Weibel. 1967. Development of fine structural damage to alveolar and capillary lining cells in oxygen-poisoned rat lungs.J. Cell. Biol. 33:605–628.

    Google Scholar 

  3. Kapanci, Y., E. R. Weibel, H. P. Kaplan andF. R. Robinson. 1969. Pathogenesis and reversibility of the pulmonary lesions of oxygen toxicity in monkeys. II. Ultrastructural and morphometric studies.Lab. Invest. 30:101–118.

    Google Scholar 

  4. Fridovich, I. 1978. The biology of oxygen radicals.Science 201:875–880.

    Google Scholar 

  5. Freeman, B. A., andJ. D. Crapo. 1981. Hyperoxia increases oxygen radical products in rat lungs and lung mitochondria.J. Biol. Chem. 256:10986–10992.

    Google Scholar 

  6. Meister, A. 1983. Selective modification of glutathione metabolism.Science 220:472–477.

    Google Scholar 

  7. Dethmers, J. K., andA. Meister. 1981. Glutathione export by human lymphoid cells: depletion of glutathione by inhibition of its synthesis decreases export and increases sensitivity to irradiation.Proc. Natl. Acad. Sci. U.S.A. 78:7492–7496.

    Google Scholar 

  8. Arrick, B. A., C. F. Nathan, O. W. Griffith, andZ. A. Cohn. 1984. Glutathione depletion sensitizes tumor cells to oxidative cytolysis.J. Biol. Chem. 257:1231–1237.

    Google Scholar 

  9. Harlan, J. M., J. D. Levine, K. S. Callahan, B. R. Schwartz, andL. W. Harker 1984. Glutathione redox cycle protects cultured endothelial cells against lysis by extracellularly generated hydrogen peroxide.J. Clin. Invest. 73:706–713.

    Google Scholar 

  10. Andreoli, S. P., C. P., Mallett, andJ. M. Bergstein. 1986. Role of glutathione in protecting endothelial cells against hydrogen peroxide oxidant injury.J. Lab. Clin. Med. 108:190–198.

    Google Scholar 

  11. Tsan, M. F., E. H. Danis, P. J. Del Vecchio, andC. L. Ropsano. 1985. Enhancement of intracellular glutathione protects endothelial cells against oxidant damage.Biochem. Biophys. Res. Commun. 127:270–276.

    Google Scholar 

  12. Kaneko, T., T. Shimokobe, O. Yoshimoto, E. Toyokawa, T. Inui, andT. Shiba. 1964. Synthesis and properties of 2-oxothiazolidine-4-carboxylic acid and its derivatives.Bull. Chem. Soc. (Japan).37:242–244.

    Google Scholar 

  13. Burchill, B. R., J. M. Oliver, C. B. Pearson, E. D. Leonbach, andR. D. Berlin. 1978. Microtubule dynamics and glutathione metabolism in phagocytising human polymorphonuclear leukocytes.J. Cell. Biol. 76:439–447.

    Google Scholar 

  14. Tietze, F. 1969. Enzymatic method for quantitative determination of nanogram amounts of total and oxidized glutathione.Anal. Biochem. 27:502–522.

    Google Scholar 

  15. Paglia, D. E., andW. N. Valentine. 1967. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase.J. Lab. Clin. Med. 70:158–169.

    Google Scholar 

  16. Horn, H. D. 1965. Glutathione reductase.In Methods of Enzymatic Analysis. H. U. Bergmeyer, editor. Verlag Chemie Academic Press, New York. 875–879.

    Google Scholar 

  17. Lowry, O. H., N. J. Rosebrough, A. L. Farr, andR. J. Randall. 1951. Protein measurement with the Folin-phenol reagent.J. Biol. Chem. 193:265–276.

    Google Scholar 

  18. Croxton, F. E. 1953. Elementary Statistics with Applications in Medicine and Biological Sciences. Dover Publications, New York. 235–244.

    Google Scholar 

  19. Griffith, O. W., andA. Meister. 1979. Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (s-n-butyl homocysteine sulfoximine).J. Biol. Chem. 254:7558–7560.

    Google Scholar 

  20. Freeman, B. A., S. L. Young, andJ. D. Crapo. 1983. Liposome-mediated augmentation of superoxide dismutase in endothelial cells prevents oxygen injury.J. Biol. Chem. 258:12534–12542.

    Google Scholar 

  21. Housset, B., C. Ody, D. B. Rubin, G. Elemer, andA. F. Junod. 1983. Oxygen toxicity in cultured aortic endothelium: Selenium-induced partial protective effect.J. Appl. Physiol. 55:343–352.

    Google Scholar 

  22. Frank, L., J. Yam, andR. J. Roberts. 1978. The role of endotoxin in protection of adult rats from oxygen-induced lung toxicity.J. Clin. Invest. 61:269–275.

    Google Scholar 

  23. Crapo, J. D., andD. F. Tierney. 1974. Superoxide dismutase and pulmonary oxygen toxicity.Am. J. Physiol. 226:1401–1407.

    Google Scholar 

  24. Turrens, J. F., J. D. Crapo, andB. A. Freeman. 1974. Protection against oxygen toxicity by intravenous injection of liposome-entrapped catalase and superoxide dismutase.J. Clin. Invest. 73:87–95.

    Google Scholar 

  25. Van Asbeck, B. S., J. Hoidal, G. M. Vercellotti, B. A. Schwartz, C. F. Moldow, andH. S. Jacob. 1985. Protection against lethal hyperoxia by tracheal insufflation of erythrocytes: Role of red cell glutathione.Science 227:756–759.

    Google Scholar 

  26. Padmnanbhan, R. V., R. Gudapaty, I. E. Liener, B. A. Schwartz, andJ. R. Hoidal. 1985. Protection against pulmonary oxygen toxicity in rats by the intratracheal administration of liposome-encapsulated superoxide dismutase or catalase.Am. Rev. Respir. Dis. 132:164–167.

    Google Scholar 

  27. Williamson, J. M., andA. Meister. 1982. New substrates of 5-oxo-prolinase.J. Biol. Chem. 257:12039–12042.

    Google Scholar 

  28. Williamson, J. M., B. Boettcher, andA. Meister. 1982. Intravenous cysteine delivery system that protects against toxicity by promoting glutathione synthesis.Proc. Natl. Acad. Sci. U.S.A. 79:6246–6249.

    Google Scholar 

  29. Williamson, J. M., andA. Meister. 1981. Stimulation of hepatic glutathione formation by administration ofl-2-oxothiazolidine-4-carboxylate, a 5-oxo-prolinase substrate.Proc. Natl. Acad. Sci. U.S.A. 78:936–939.

    Google Scholar 

  30. Russo, A., andJ. B. Mitchell. 1985. Potentiation and protection of adriamycin cytotoxicity by cellular glutathione modulation.Cancer Treat Rep. 69:1293–1296.

    Google Scholar 

  31. Russo, A., W. DeGraff, N. Friedman, andJ. B. Mitchell. 1986. Selective modulation of glutathione levels in human normal versus tumor cells and subsequent differential response to chemotherapy drugs.Cancer Res. 46:2845–2848.

    Google Scholar 

  32. Russo, A., J. B. Mitchell, S. J. McPherson, andN. Friedman. 1984. Alteration of bleomycin cytotoxicity by glutathione depletion or elevation.Int. J. Radiat. Oncol. Biol. Phys. 10:1675–1678.

    Google Scholar 

  33. Passero, M. A., andC. Carmody. 1986.l-2-Oxothiazolidine-4-carboxylic acid increases glutathione in mouse lung.Am. Rev. Respir. Dis. 133:396A.

    Google Scholar 

  34. Katzenstein, A., C. M. Bloor, andA. A. Leibow. 1976. Diffuse alveolar damage-the role of oxygen, shock and related factors.Am. J. Palhol. 85:210–228.

    Google Scholar 

  35. Shasby, D. M., R. B. Fox, R. N. Harada, andJ. E. Repine. 1982. Reduction of the edema of acute hyperoxic lung injury by granulocyte depletion.J. Appl. Physiol. 52:1237–1244.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Service, Veterans Administration Medical Center Departments of Physiology and Medicine, Albany Medical College of Union University, 12208, Albany, New York

    Min-Fu Tsan & Patricia G. Phillips

Authors
  1. Min-Fu Tsan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patricia G. Phillips
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This work was in part supported by the Veterans Administration Medical Research Service and a grant from the U.S. Public Health Service HL 32418. Dr. Phillips is supported by a Postdoctoral Training Grant HL 07529.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tsan, MF., Phillips, P.G. L-2-Oxothiazolidine-4-carboxylate protects cultured endothelial cells against hyperoxia-induced injury. Inflammation 12, 113–121 (1988). https://doi.org/10.1007/BF00916394

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00916394

Keywords

Search

Navigation