Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1983 Apr 15;212(1):39–44. doi: 10.1042/bj2120039

The effect of cysteine oxidation on isolated hepatocytes.

J Viña, G T Saez, D Wiggins, A F Roberts, R Hems, H A Krebs
PMCID: PMC1152007  PMID: 6870855

Abstract

Isolated hepatocytes incubated with 4mM-cysteine lose reduced glutathione, adenine nucleotides and intracellular enzymes, thus showing extensive membrane damage. The toxic effects of cysteine are enhanced by NH4Cl. Lactate, ethanol and unsaturated fatty acids afford significant protection against cysteine-induced cytoxicity. Addition of catalase to the incubation medium also protected against cysteine toxicity, indicating that H2O2 formed during the oxidation of cysteine is involved in the toxic effects observed. Under anaerobic conditions cysteine did not cause leakage of lactate dehydrogenase from cells, confirming that rapid autoxidation is an essential condition for development of the toxic effects of cysteine.

Full text

PDF
39

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BIRNBAUM S. M., WINITZ M., GREENSTEIN J. P. Quantitative nutritional studies with water-soluble, chemically defined diets. III. Individual amino acids as sources of non-essential nitrogen. Arch Biochem Biophys. 1957 Dec;72(2):428–436. doi: 10.1016/0003-9861(57)90218-7. [DOI] [PubMed] [Google Scholar]
  2. Beatty P., Reed D. J. Influence of cysteine upon the glutathione status of isolated rat hepatocytes. Biochem Pharmacol. 1981 Jun 1;30(11):1227–1230. doi: 10.1016/0006-2952(81)90302-6. [DOI] [PubMed] [Google Scholar]
  3. Beauchamp C., Fridovich I. A mechanism for the production of ethylene from methional. The generation of the hydroxyl radical by xanthine oxidase. J Biol Chem. 1970 Sep 25;245(18):4641–4646. [PubMed] [Google Scholar]
  4. Berry M. N., Friend D. S. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol. 1969 Dec;43(3):506–520. doi: 10.1083/jcb.43.3.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Christophersen B. O. Formation of monohydroxy-polyenic fatty acids from lipid peroxides by a glutathione peroxidase. Biochim Biophys Acta. 1968 Sep 2;164(1):35–46. doi: 10.1016/0005-2760(68)90068-4. [DOI] [PubMed] [Google Scholar]
  6. Fridovich I. Superoxide dismutases. Adv Enzymol Relat Areas Mol Biol. 1974;41(0):35–97. doi: 10.1002/9780470122860.ch2. [DOI] [PubMed] [Google Scholar]
  7. Högberg J., Kristoferson A. A correlation between glutathione levels and cellular damage in isolated hepatocytes. Eur J Biochem. 1977 Mar 15;74(1):77–82. doi: 10.1111/j.1432-1033.1977.tb11368.x. [DOI] [PubMed] [Google Scholar]
  8. Krebs H. A., Freedland R. A., Hems R., Stubbs M. Inhibition of hepatic gluconeogenesis by ethanol. Biochem J. 1969 Mar;112(1):117–124. doi: 10.1042/bj1120117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Nishiuch Y., Sasaki M., Nakayasu M., Oikawa A. Cytotoxicity of cysteine in culture media. In Vitro. 1976 Sep;12(9):635–638. doi: 10.1007/BF02797462. [DOI] [PubMed] [Google Scholar]
  10. Olney J. W., Ho O. L., Rhee V. Cytotoxic effects of acidic and sulphur containing amino acids on the infant mouse central nervous system. Exp Brain Res. 1971;14(1):61–76. doi: 10.1007/BF00234911. [DOI] [PubMed] [Google Scholar]
  11. Piperno E., Berssenbruegge D. A. Reversal of experimental paracetamol toxicosis with N-acetylcysteine. Lancet. 1976 Oct 2;2(7988):738–739. doi: 10.1016/s0140-6736(76)90030-1. [DOI] [PubMed] [Google Scholar]
  12. Prescott L. F., Park J., Ballantyne A., Adriaenssens P., Proudfoot A. T. Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet. 1977 Aug 27;2(8035):432–434. doi: 10.1016/s0140-6736(77)90612-2. [DOI] [PubMed] [Google Scholar]
  13. RACKER E. The mechanism of action of glyoxalase. J Biol Chem. 1951 Jun;190(2):685–696. [PubMed] [Google Scholar]
  14. THEORELL H., YONETANI T. LIVER ALCOHOL DEHYDROGENASE-DPN-PYRAZOLE COMPLEX: A MODEL OF A TERNARY INTERMEDIATE IN THE ENZYME REACTION. Biochem Z. 1963;338:537–553. [PubMed] [Google Scholar]
  15. TSEN C. C., TAPPEL A. L. Catalytic oxidation of glutathione and other sulfhydryl compounds by selenite. J Biol Chem. 1958 Nov;233(5):1230–1232. [PubMed] [Google Scholar]
  16. Theorell H. Function and structure of liver alcohol dehydrogenase. Harvey Lect. 1967;61:17–41. [PubMed] [Google Scholar]
  17. Thor H., Moldéus P., Kristoferson A., Högberg J., Reed D. J., Orrenius S. Metabolic activation and hepatotoxicity. Metabolism of bromobenzene in isolated hypatocytes. Arch Biochem Biophys. 1978 May;188(1):114–121. doi: 10.1016/0003-9861(78)90363-6. [DOI] [PubMed] [Google Scholar]
  18. Thor H., Moldéus P., Orrenius S. Metabolic activation and hepatotoxicity. Effect of cysteine, N-acetylcysteine, and methionine on glutathione biosynthesis and bromobenzene toxicity in isolated rat hepatocytes. Arch Biochem Biophys. 1979 Feb;192(2):405–413. doi: 10.1016/0003-9861(79)90109-7. [DOI] [PubMed] [Google Scholar]
  19. Viña J., Hems R., Krebs H. A. Maintenance of glutathione content is isolated hepatocyctes. Biochem J. 1978 Mar 15;170(3):627–630. doi: 10.1042/bj1700627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Viña J., Romero F. J., Estrela J. M., Viña J. R. Effect of acetaminophen (paracetamol) and its antagonists on glutathione (GSH) content in rat liver. Biochem Pharmacol. 1980 Jul 1;29(13):1968–1970. doi: 10.1016/0006-2952(80)90113-6. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES