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. 1992 Aug;45(8):679–683. doi: 10.1136/jcp.45.8.679

Glutathione S-transferases in neonatal liver disease.

J Mathew 1, A R Cattan 1, A G Hall 1, J E Hines 1, R Nelson 1, E Eastham 1, A D Burt 1
PMCID: PMC495143  PMID: 1401176

Abstract

AIMS: To investigate the distribution of alpha and pi class glutathione S-transferases (GST) in normal fetal, neonatal, and adult liver; and to examine changes in GST expression in neonatal liver disease. METHODS: alpha and pi class GST were immunolocalised in sections of formalin fixed liver tissue obtained from human fetuses (n = 21), neonates (n = 8), young children (n = 9) and adults (n = 10), and from neonates with extrahepatic biliary atresia (n = 15) and neonatal hepatitis (n = 12). Monospecific rabbit polyclonal antibodies were used with a peroxidase-antiperoxidase method. RESULTS: Expression of pi GST was localised predominantly within biliary epithelial cells of developing and mature bile ducts of all sizes from 16 weeks' gestation until term and in neonatal and adult liver. Coexpression of pi and alpha GST was seen in hepatocytes of developing fetal liver between 16 and 34 weeks' gestation. Although pi GST was seen in occasional hepatocytes up to six months of life, this isoenzyme was not expressed by hepatocytes in adult liver. By contrast, alpha GST continued to be expressed by hepatocytes in adult liver; this isoenzyme was also seen in some epithelial cells of large bile ducts in adult liver. No change was observed in the distribution of alpha GST in either neonatal hepatitis or extrahepatic biliary atresia. However, aberrant expression of pi GST was identified in hepatocytes of all but one case of extrahepatic biliary atresia but in only two cases of neonatal hepatitis. CONCLUSIONS: The phenotypic alterations noted in extrahepatic biliary atresia may result from the effect of cholate stasis. Evaluation of the pattern of pi and alpha GST distribution by immunohistochemical staining may provide valuable information in distinguishing between these two forms of neonatal liver disease.

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Selected References

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  1. Adachi Y., Horii K., Takahashi Y., Tanihata M., Ohba Y., Yamamoto T. Serum glutathione S-transferase activity in liver diseases. Clin Chim Acta. 1980 Oct 9;106(3):243–255. doi: 10.1016/0009-8981(80)90308-3. [DOI] [PubMed] [Google Scholar]
  2. Beckett G. J., Dyson E. H., Chapman B. J., Templeton A. J., Hayes J. D. Plasma glutathione S-transferase measurements by radioimmunoassay: a sensitive index of hepatocellular damage in man. Clin Chim Acta. 1985 Feb 28;146(1):11–19. doi: 10.1016/0009-8981(85)90119-6. [DOI] [PubMed] [Google Scholar]
  3. Beckett G. J., Foster G. R., Hussey A. J., Oliveira D. B., Donovan J. W., Prescott L. F., Proudfoot A. T. Plasma glutathione S-transferase and F protein are more sensitive than alanine aminotransferase as markers of paracetamol (acetaminophen)-induced liver damage. Clin Chem. 1989 Nov;35(11):2186–2189. [PubMed] [Google Scholar]
  4. Beckett G. J., Hayes P. C., Hussey A. J., Bouchier I. A., Hayes J. D. Plasma glutathione S-transferase measurements in patients with alcoholic cirrhosis. Clin Chim Acta. 1987 Oct 30;169(1):85–89. doi: 10.1016/0009-8981(87)90396-2. [DOI] [PubMed] [Google Scholar]
  5. Brough A. J., Bernstein J. Conjugated hyperbilirubinemia in early infancy. A reassessment of liver biopsy. Hum Pathol. 1974 Sep;5(5):507–516. doi: 10.1016/s0046-8177(74)80003-1. [DOI] [PubMed] [Google Scholar]
  6. Chasseaud L. F. The role of glutathione and glutathione S-transferases in the metabolism of chemical carcinogens and other electrophilic agents. Adv Cancer Res. 1979;29:175–274. doi: 10.1016/s0065-230x(08)60848-9. [DOI] [PubMed] [Google Scholar]
  7. Desmet V. J. Cholangiopathies: past, present, and future. Semin Liver Dis. 1987 May;7(2):67–76. doi: 10.1055/s-2008-1040566. [DOI] [PubMed] [Google Scholar]
  8. Hall A., Foster S., Proctor S. J., Cattan A. R. Purification and characterization of a pi class glutathione S-transferase from human leukaemic cells. Br J Haematol. 1990 Dec;76(4):494–500. doi: 10.1111/j.1365-2141.1990.tb07906.x. [DOI] [PubMed] [Google Scholar]
  9. Harrison D. J., May L., Hayes P. C., Haque M. M., Hayes J. D. Glutathione S-transferases in alcoholic liver disease. Gut. 1990 Aug;31(8):909–912. doi: 10.1136/gut.31.8.909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hayes P. C., Harrison D. J., Bouchier I. A., McLellan L. I., Hayes J. D. Cytosolic and microsomal glutathione S-transferase isoenzymes in normal human liver and intestinal epithelium. Gut. 1989 Jun;30(6):854–859. doi: 10.1136/gut.30.6.854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hayes P. C., Hussey A. J., Keating J., Bouchier I. A., Williams R., Beckett G. J., Hayes J. D. Glutathione S-transferase levels in autoimmune chronic active hepatitis: a more sensitive index of hepatocellular damage than aspartate transaminase. Clin Chim Acta. 1988 Mar 15;172(2-3):211–216. doi: 10.1016/0009-8981(88)90325-7. [DOI] [PubMed] [Google Scholar]
  12. Hiley C., Fryer A., Bell J., Hume R., Strange R. C. The human glutathione S-transferases. Immunohistochemical studies of the developmental expression of Alpha- and Pi-class isoenzymes in liver. Biochem J. 1988 Aug 15;254(1):255–259. doi: 10.1042/bj2540255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Howie A. F., Patrick A. W., Fisher B. M., Collier A., Frier B. M., Beckett G. J. Plasma hepatic glutathione S-transferase concentrations after insulin-induced hypoglycaemia in normal subjects and diabetic patients. Diabet Med. 1989 Apr;6(3):224–227. doi: 10.1111/j.1464-5491.1989.tb01151.x. [DOI] [PubMed] [Google Scholar]
  14. Kaplowitz N. Physiological significance of glutathione S-transferases. Am J Physiol. 1980 Dec;239(6):G439–G444. doi: 10.1152/ajpgi.1980.239.6.G439. [DOI] [PubMed] [Google Scholar]
  15. Mannervik B. The isoenzymes of glutathione transferase. Adv Enzymol Relat Areas Mol Biol. 1985;57:357–417. doi: 10.1002/9780470123034.ch5. [DOI] [PubMed] [Google Scholar]
  16. Randall B. J., Angus B., Akiba R., Hall A., Cattan A. R., Proctor S. J., Jones R. A., Horne C. H. Glutathione S-transferase (placental) as a marker of transformation in the human cervix uteri: an immunohistochemical study. Br J Cancer. 1990 Oct;62(4):614–618. doi: 10.1038/bjc.1990.340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Raweily E. A., Gibson A. A., Burt A. D. Abnormalities of intrahepatic bile ducts in extrahepatic biliary atresia. Histopathology. 1990 Dec;17(6):521–527. doi: 10.1111/j.1365-2559.1990.tb00791.x. [DOI] [PubMed] [Google Scholar]
  18. Strange R. C., Davis B. A., Faulder C. G., Cotton W., Bain A. D., Hopkinson D. A., Hume R. The human glutathione S-transferases: developmental aspects of the GST1, GST2, and GST3 loci. Biochem Genet. 1985 Dec;23(11-12):1011–1028. doi: 10.1007/BF00499944. [DOI] [PubMed] [Google Scholar]
  19. Strange R. C., Faulder C. G., Davis B. A., Hume R., Brown J. A., Cotton W., Hopkinson D. A. The human glutathione S-transferases: studies on the tissue distribution and genetic variation of the GST1, GST2 and GST3 isozymes. Ann Hum Genet. 1984 Jan;48(Pt 1):11–20. doi: 10.1111/j.1469-1809.1984.tb00829.x. [DOI] [PubMed] [Google Scholar]
  20. Terrier P., Townsend A. J., Coindre J. M., Triche T. J., Cowan K. H. An immunohistochemical study of pi class glutathione S-transferase expression in normal human tissue. Am J Pathol. 1990 Oct;137(4):845–853. [PMC free article] [PubMed] [Google Scholar]

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