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. 1981 Jan;67(1):51–59. doi: 10.1172/JCI110032

Various enzyme activities in muscle and other organs of dystrophic mice.

T Aoyagi, T Wada, F Kojima, M Nagai, H Umezawa
PMCID: PMC371571  PMID: 6256414

Abstract

To elucidate the metabolic abnormality of musclar dystrophy, 27 kinds of enzyme activity in various organs of control and dystrophic mice were examined. The organs examined included muscle, bone, heart, testis, uterus, spleen, thymus, submaxillary gland, stomach, pancreas, liver, kidney, brain, and lung. The activities of 14 different aminopeptidases, 5 endopeptidases, 4 glycosidases, phosphatase, esterase, and ribonuclease were measured. Most of the enzyme activities were significantly elevated in muscles and bones of dystrophic mice. These organs were similar in their patterns of enzyme abnormality. Among the 14 kinds of aminopeptidase activity studied, the degree of increased activity was greater for the aminopeptidases (AP):Ala-AP, Leu-AP, Met-AP, Phe-AP, Trp-AP, Gly-Pro-Leu-AP. In addition to aminopeptidases, there were significant increases in activities of chymotrypsinlike enzyme, cathepsin C, cathepsin D, several glycosidases and neutral ribonuclease in the muscles of dystrophic mice. Similarly increased enzyme activity was also observed in organs other than muscle and bone. Furthermore, protein content in most organs was higher in dystrophic mice than in those of control mice. These abnormalities were seen in both males and females. The present results suggest that there are extensive abnormalities in the protein metabolism in dystrophic mice. It seems therefore that the therapeutic approach to muscular dystrophy should be studies not only from the well-known abnormality of intramuscular endopeptidases, but from other aspects as well.

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Selected References

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

  1. Aoyagi T., Kunimoto S., Morishima H., Takeuchi T., Umezawa H. Effect of pepstatin on acid proteases. J Antibiot (Tokyo) 1971 Oct;24(10):687–694. doi: 10.7164/antibiotics.24.687. [DOI] [PubMed] [Google Scholar]
  2. Aoyagi T., Nagai M., Iwabuchi M., Liaw W. S., Andoh T., Umezawa H. Aminopeptidase activities on the surface of mammalian cells and their alterations associated with transformation. Cancer Res. 1978 Oct;38(10):3505–3508. [PubMed] [Google Scholar]
  3. Aoyagi T., Nerome K., Suzuki J., Takeuchi T., Umezawa H. Change of enzyme activities during the early stage of influenza virus infection. Biochem Biophys Res Commun. 1974 Oct 8;60(3):1178–1184. doi: 10.1016/0006-291x(74)90436-7. [DOI] [PubMed] [Google Scholar]
  4. Aoyagi T., Suda H., Nagai M., Ogawa K., Suzuki J. Aminopeptidase activities on the surface of mammalian cells. Biochim Biophys Acta. 1976 Nov 8;452(1):131–143. doi: 10.1016/0005-2744(76)90064-4. [DOI] [PubMed] [Google Scholar]
  5. Aoyagi T., Suda H., Nagai M., Tobe H., Suzuki J., Takeuchi T., Umezawa H. Release of a plasma membrane-bound triaminopeptidase activity from mammalian cells by thermolysin. Biochem Biophys Res Commun. 1978 Jan 30;80(2):435–442. doi: 10.1016/0006-291x(78)90696-4. [DOI] [PubMed] [Google Scholar]
  6. Iodice A. A. The inhibition by pepstatin of cathepsin D and autolysis of dystrophic muscle. Life Sci. 1976 Nov 1;19(9):1351–1358. doi: 10.1016/0024-3205(76)90433-1. [DOI] [PubMed] [Google Scholar]
  7. Ishiura S., Murofushi H., Suzuki K., Imahori K. Studies of a calcium-activated neutral protease from chicken skeletal muscle. I. Purification and characterization. J Biochem. 1978 Jul;84(1):225–230. doi: 10.1093/oxfordjournals.jbchem.a132111. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Libby P., Goldberg A. L. Leupeptin, a protease inhibitor, decreases protein degradation in normal and diseased muscles. Science. 1978 Feb 3;199(4328):534–536. doi: 10.1126/science.622552. [DOI] [PubMed] [Google Scholar]
  10. McGowan E. B., Shafiq S. A., Stracher A. Delayed degeneration of dystrophic and normal muscle cell cultures treated with pepstatin, leupeptin, and antipain. Exp Neurol. 1976 Mar;50(3):649–657. doi: 10.1016/0014-4886(76)90034-0. [DOI] [PubMed] [Google Scholar]
  11. Sanada Y., Yasogawa N., Katunuma N. Serine protease in mice with hereditary muscular dystrophy. J Biochem. 1978 Jan;83(1):27–33. doi: 10.1093/oxfordjournals.jbchem.a131901. [DOI] [PubMed] [Google Scholar]
  12. Schorr E. E., Arnason B. G., Aström K. E., Darzynkiewicz Z. Treatment of mouse muscular dystrophy with the protease inhibitor pepstatin. J Neuropathol Exp Neurol. 1978 May;37(3):263–268. doi: 10.1097/00005072-197805000-00004. [DOI] [PubMed] [Google Scholar]
  13. Stracher A., McGowan E. B., Hedrych A., Shafiq S. A. In vivo effect of protease inhibitors in denervation atrophy. Exp Neurol. 1979 Dec;66(3):611–618. doi: 10.1016/0014-4886(79)90206-1. [DOI] [PubMed] [Google Scholar]
  14. Stracher A., McGowan E. B., Shafiq S. A. Muscular dystrophy: inhibition of degeneration in vivo with protease inhibitors. Science. 1978 Apr 7;200(4337):50–51. doi: 10.1126/science.635570. [DOI] [PubMed] [Google Scholar]
  15. Tobe H., Kojima F., Aoyagi T., Umezawa H. Purification by affinity chromatography using amastatin and properties of aminopeptidase A from pig kidney. Biochim Biophys Acta. 1980 Jun 13;613(2):459–468. doi: 10.1016/0005-2744(80)90100-x. [DOI] [PubMed] [Google Scholar]
  16. Toyo-Oka T., Shimizu T., Masaki T. Inhibition of proteolytic activity of calcium activated neutral protease by leupeptin and antipain. Biochem Biophys Res Commun. 1978 May 30;82(2):484–491. doi: 10.1016/0006-291x(78)90900-2. [DOI] [PubMed] [Google Scholar]
  17. Umezawa H., Aoyagi T., Suda H., Hamada M., Takeuchi T. Bestatin, an inhibitor of aminopeptidase B, produced by actinomycetes. J Antibiot (Tokyo) 1976 Jan;29(1):97–99. doi: 10.7164/antibiotics.29.97. [DOI] [PubMed] [Google Scholar]

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