Summary
In the previous experiments, it was demonstrated that high purity elastase extracted from porcine pancreas remarkably inhibits liver fibrosis of rats having chronic liver injury caused by carbon tetrachloride. This time, with the purpose to clarify the mechanism of inhibition of liver fibrosis by elastase, comparative study was made on the activity of lysosomal enzymes by measuring β-glucuronidase, cathepsin and collagenolytic activity, with the rats administered with elastase and with those untreated, during the period of development of liver fibrosis and the recovery from it.
In addition to it, in vitro experiments were made by having elastase act on the substrate comprising mixed collagen of acid soluble and neutral soluble collagens extracted from the skin of guinea pig and by observing collagen components by disc electrophoresis.
With any lysosomal enzymes, no marked difference was noticed between elastase group and non-administered group and thus the possibility of inhibition of liver fibrosis through activation of lysosomal enzyme by elastase was denied. The results of disc electrophoretic observation of the performance of elastase on collagen revealed that β-component of collagen is disappeared but α-component remained. From the above, inhibition of liver fibrosis by elastase may be due to direct affection of elastase to telopetide portion of collagen.
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Tsujii, T., Fukuhara, M., Matsumori, T., Tamura, M., Matsui, T. and Morita, T.: Studies on the inhibition of experimental liver fibrosis. 1. Effect of elastase on the liver fibrosis of rats due to carbon tetrachloride. Gastroenterologia Japonica. 9: 145–154, 1974.
Oda, T. and Yokono, O.: Lysosome in hepatic cell. Metabolism and Disease. 5: 828–834, 1968.
Fishman, W.H.: Application of an improved glucuronidase assay method to the study of human blood β-glucuronidase. J.B.C. 173: 449–456, 1948.
Anson, M.L.: The estimation of pepsin, trypsin, papain, and cathepsin with hemoglobin. J. Gen. Physiol. 22: 79–89, 1938.
Frankland, D.M. and Wynn, C.H.: The degradation of acid-soluble collagen by rat-liver preparations. Biochem. J. 85: 276–282, 1962.
Jackson, D.S.: Connective tissue growth stimulated by carrageenin. Biochem. J. 65: 277–284, 1957.
Sakai, T. and Gross, J.: Some properties of the products of reaction of tadopole collagenase with collagen. Biochemistry. 6: 518–528, 1967.
Balo, J. and Banga, I.: The elastolytic activity of pancreatic extracts. Biochem. J. 46: 384–387, 1950.
Grant, H. and Alburn, H.E.: Studies on the collagenase of clostridium histolyticum. Arch. Biochem. Biophys. 82: 245–255, 1959.
Shikata, T., Kanetaka, T. and Sakai, T.: Proliferation of elastic fibers in the liver. Saishin Igaku. 24: 38–45, 1969.
Igarashi, S., Sakai, T., Oda, T. and Fujiwara, K.: Biochemical analysis of the collagen and elastin from cirrhotic human liver. Acta Hepatologica Japo. 13: 691–695, 1972.
Brown, P.C., Consden, R. and Glynn, L.E.: Observation on the shrink temperature of collagen and its variations with age and disease. Ann. Rheum. Disease. 17: 196–208, 1958.
Schaub, M.C.: A collagen degrading mechanism in the rat uterus during post partum involution. Helv. Physiol. Acta. 21: 227–238, 1963.
Ungar, H. and Feldman, J.D.: Histologic changes accompanying the absorption of implanted surgical gut in the liver. Am. J. Path. 29: 963–967, 1953.
Fujiwara, K., Sakai, T., Oda, T. and Igarashi, S.: The presence of collagenase in kupffer cells of the rat liver. Biochem. Biophys. Res. Comm. 54: 531–537, 1973.
Nakano, H. and Ito, K.: Hepatic collagenase activity in experimental liver fibrosis. Acta Hepatologica Japo. 13: 161–163, 1972.
Hirayama, C, Hiroshige, K. and Masuya, T.: Hepatic collagenolytic activity in rats after carbontetrachloride poisoning. Biochem. J. 115: 843–847, 1969.
Oshima, Y. and Otaka, Y.: Connective tissue disease. 1st ed., Igakushoin LTD, Tokyo, Japan, 1969, p. 41.
Woessner, J.F. Jr.: Treaties on collagen. Acad. Press, New York, USA, 1968, p. 253.
Lucy, J.A., Dingle, J.T. and Fell, H.B.: Studies on the mode of action of excess of vitamin A. Biochem. J. 79: 500–508, 1961.
Hoffman, P., Linker, A., Lippman, V. and Meyer, K.: The structure of chondroitin sulfate B from studies with flavobacterium enzymes. J. Biol. Chem. 235: 3066–3069, 1960.
Oda, M.: Mechanism of liver fibrosis. Acta Hepatologica Japo. 10: 501–529, 1969.
Hutterer, F.: Degradation of mucopolysaccharides by hepatic lysosomes. Biochim. Biophys. Acta. 115: 312–319, 1966.
Lewis, U.J., Willams, D.E. and Brink, N.G.: Pancreatic elastase purification properties and function. J. Biol. Chem. 222: 705–720, 1956.
Grant, N.H. and Alburn, H.E.: Collagen solubilized by mammalian proteinase. Arch. Biochem. Biophys. 89: 262–270, 1960.
Partridge, S.M. and Davis, H.E.: The chemistry of connective tissue. 3. Component of the soluble proteins derived from elastin. Biochem. J. 61: 21–30, 1955.
Naughton, M.A. and Sanger, F.: Purification and specificity of pancreatic elastase. Biochem. J. 78: 156–163, 1961.
Bornstein, P. and Piez, K.A.: The nature of the intramolecular cross-links in collagen. The separation and characterization of peptides from the crosslink region of rat skin collagen. Biochemistry. 5: 3460–3473, 1966.
Kang, A.H., Bornstein, P. and Piez, K.A.: The amino acid sequence of peptides from the corsslikage region of rat skin collagen. Biochemistry. 6: 788–795, 1967.
Bornstein, P.: The incomplete hydroxylation of individual prolyl residues in collagen. J. Biol. Chem. 242: 2572–2574, 1967.
Davison, P.F.: Action of proteolytic enzymes on tropocollagen and insoluble collagen. Biochemistry. 5: 301–312, 1966.
Sakai, T. Biochemistry of collagen. Saishin Igaku. 24: 156–163, 1969.
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Tsujii, T., Fukuhara, M., Fukuda, S. et al. Studies on the inhibition of experimental liver fibrosis. Gastroenterol Jpn 10, 215–220 (1975). https://doi.org/10.1007/BF02776655
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DOI: https://doi.org/10.1007/BF02776655