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. 1979 Oct;20(10):825–832. doi: 10.1136/gut.20.10.825

Hepatic prolyl hydroxylase and collagen synthesis in patients with alcoholic liver disease

S W Mann, G C Fuller, J V Rodil, Eva I Vidins
PMCID: PMC1412715  PMID: 230128

Abstract

Hepatic prolyl hydroxylase activity and collagen synthesis were measured in patients with alcoholic liver disease to determine the feasibility of using the enzyme prolyl hydroxylase as a marker of hepatic fibrogenesis. Alcoholic patients with liver histopathology consistent with normal, steatosis, alcoholic hepatitis, early cirrhosis, or advanced cirrhosis were analysed for liver prolyl hydroxylase activity and in vitro collagen synthesis. Prolyl hydroxylase activity and the rate of in vitro collagen synthesis were correlated when these parameters were measured in samples of the same liver biopsy. Mean prolyl hydroxylase activity was significantly raised in all groups of alcoholic patients with alcoholic liver disease, except those with steatosis, when compared with alcoholic patients with normal morphology. Alcoholic patients with early cirrhosis had enzyme activity (mean ± SE: 1·367 ±0·162 mU/mg protein) significantly raised over all other groups. Mean enzyme activity was less raised (0·985 ± 0·097 mU/mg protein) in patients with advanced cirrhosis. The percentage of collagen synthesis in patients with early or advanced cirrhosis was also raised compared with alcoholic patients with normal morphology. Prolyl hydroxylase activity and the rate of collagen synthesis are significantly correlated (r=0·62). These findings suggest that hepatic prolyl hydroxylase activity is a useful indicator of hepatic fibrogenesis and its measurement on available liver biopsy tissue should be a potent diagnostic tool reflecting active fibrogenesis and predicting progression of alcoholic liverdisease.

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Selected References

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

  1. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cardinale G. J., Udenfriend S. Prolyl hydroxylase. Adv Enzymol Relat Areas Mol Biol. 1974;41(0):245–300. doi: 10.1002/9780470122860.ch6. [DOI] [PubMed] [Google Scholar]
  3. Chen T. S., Leevy C. M. Collagen biosynthesis in liver disease of the alcoholic. J Lab Clin Med. 1975 Jan;85(1):103–112. [PubMed] [Google Scholar]
  4. Diegelmann R. F., Rothkopf L. C., Cohen I. K. Measurement of collagen biosynthesis during wound healing. J Surg Res. 1975 Oct;19(4):239–243. doi: 10.1016/0022-4804(75)90087-6. [DOI] [PubMed] [Google Scholar]
  5. Fuller G. C., Nolan J. C. Prolyl hydroxylase activity in normal and diseased human liver. Proc Soc Exp Biol Med. 1976 Jan;151(1):61–64. doi: 10.3181/00379727-151-39143. [DOI] [PubMed] [Google Scholar]
  6. Goldberg S. J., Mendenhall C. L., Connell A. M., Chedid A. "Nonalcoholic" chronic hepatitis in the alcoholic. Gastroenterology. 1977 Apr;72(4 Pt 1):598–604. [PubMed] [Google Scholar]
  7. Grant M. E., Prockop D. J. The biosynthesis of collagen. 1. N Engl J Med. 1972 Jan 27;286(4):194–199. doi: 10.1056/NEJM197201272860406. [DOI] [PubMed] [Google Scholar]
  8. Huberman A., Recio A., Rojkind M. Collagen biosynthesis in normal and cirrhotic rat liver slices. Proc Soc Exp Biol Med. 1969 May;131(1):200–203. doi: 10.3181/00379727-131-33839. [DOI] [PubMed] [Google Scholar]
  9. Jain S., Scheuer P. J., McGee J. O., Sherlock S. Hepatic collagen proline hydroxylase activity in primary biliary cirrhosis. Eur J Clin Invest. 1978 Feb;8(1):15–17. doi: 10.1111/j.1365-2362.1978.tb00802.x. [DOI] [PubMed] [Google Scholar]
  10. KENT G., FELS I. G., DUBIN A., POPPER H. Collagen content based on hydroxyproline determinations in human and rat livers; its relation to morphologically demonstrable reticulum and collagen fibers. Lab Invest. 1959 Jan-Feb;8(1):48–56. [PubMed] [Google Scholar]
  11. Kershenobich D., Fierro F. J., Rojkind M. The relationship between the free pool of proline and collagen content in human liver cirrhosis. J Clin Invest. 1970 Dec;49(12):2246–2249. doi: 10.1172/JCI106443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  13. McGee J. O., Patrick R. S., Rodger M. C., Luty C. M. Collagen proline hydroxylase activity and 35S sulphate uptake in human liver biopsies. Gut. 1974 Apr;15(4):260–267. doi: 10.1136/gut.15.4.260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. McGee J. O., Patrick R. S. The role of perisinusoidal cells in hepatic fibrogenesis. An electron microscopic study of acute carbon tetrachloride liver injury. Lab Invest. 1972 Apr;26(4):429–440. [PubMed] [Google Scholar]
  15. Mezey E., Imbembo A. L. Hepatic collagen proline hydroxylase activity in hepatic disease following jejunoileal bypass for morbid obesity. Surgery. 1978 Mar;83(3):345–353. [PubMed] [Google Scholar]
  16. Mezey E., Potter J. J., Iber F. L., Maddrey W. C. Hepatic collagen proline hydroxylase activity in alcoholic hepatitis: effect of d-penicillamine. J Lab Clin Med. 1979 Jan;93(1):92–100. [PubMed] [Google Scholar]
  17. Mezey E., Potter J. J., Maddrey W. C. Hepatic collagen proline hydroxylase activity in alcoholic liver disease. Clin Chim Acta. 1976 May 3;68(3):313–320. doi: 10.1016/0009-8981(76)90397-1. [DOI] [PubMed] [Google Scholar]
  18. Peterkofsky B., Diegelmann R. Use of a mixture of proteinase-free collagenases for the specific assay of radioactive collagen in the presence of other proteins. Biochemistry. 1971 Mar 16;10(6):988–994. doi: 10.1021/bi00782a009. [DOI] [PubMed] [Google Scholar]
  19. Popper H., Uenfriend S. Hepatic fibrosis. Correlation of biochemical and morphologic investigations. Am J Med. 1970 Nov;49:707–721. doi: 10.1016/s0002-9343(70)80135-8. [DOI] [PubMed] [Google Scholar]
  20. Rhoads R. E., Udenfriend S. Purification and properties of collagen proline hydroxylase from newborn rat skin. Arch Biochem Biophys. 1970 Aug;139(2):329–339. doi: 10.1016/0003-9861(70)90485-6. [DOI] [PubMed] [Google Scholar]
  21. Risteli J., Tuderman L., Kivirikko K. I. Intracellular enzymes of collagen biosynthesis in rat liver as a function of age and in hepatic injury induced by dimethylnitrosamine. Purification of rat prolyl hydroxylase and comparison of changes in prolyl hydroxylase activity with changes in immunoreactive prolyl hydroxylase. Biochem J. 1976 Aug 15;158(2):369–376. doi: 10.1042/bj1580369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rojkind M., Diaz de León L. Collagen biosynthesis in cirrhotic rat liver slices a regulatory mechanism. Biochim Biophys Acta. 1970 Oct 15;217(2):512–522. doi: 10.1016/0005-2787(70)90548-4. [DOI] [PubMed] [Google Scholar]
  23. Scheuer P. J. Liver biopsy in the diagnosis of cirrhosis. Gut. 1970 Mar;11(3):275–278. doi: 10.1136/gut.11.3.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Shaba J. K., Patrick R. S., McGee J. O. Collagen synthesis by mesenchymal cells isolated from normal and acutely-damaged mouse liver. Br J Exp Pathol. 1973 Feb;54(1):110–116. [PMC free article] [PubMed] [Google Scholar]
  25. Takeuchi T., Prockop D. J. Protocollagen proline hydroxylase in normal liver and in hepatic fibrosis. Gastroenterology. 1969 Apr;56(4):744–750. [PubMed] [Google Scholar]

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