The Role of Lysosomes and Microtubules in Cardiac Protein Degradation

  • K. Wildenthal
  • J. S. Crie
  • J. M. Ord
  • J. R. Wakeland
Part of the Advances in Myocardiology book series (ADMY)

Abstract

The mechanisms and regulatory factors involved in cardiac proteolysis are incom- pletely understo0d. Agents that interfere with lysosomal function (e.g., chloroquine, leupeptin, methyladenine) cause a 25–30% reduction in the overall rate of protein degradation. In the same hearts, however, the rate of myosin breakdown remains unchanged. Disaggregation of microtubules with colchicine is accompanied by a 15% reduction in the rate of degradation of total protein and of myosin. In the same hearts, the degradation of “organellar” protein, including mitochondrial cytochromes, is reduced by over 30%. Thus, it appears that the degradation of different classes of cardiac proteins may be accomplished and regulated by different processes. Lysosomes are important in overall proteolysis, but appear not to be involved in the regulation of myosin breakdown. Microtubules are also involved in the proteolytic process, and appear to be especially important for the breakdown of proteins from mitochondria and perhaps other organelles.

Keywords

Protein Degradation Autophagic Vacuole Myofibrillar Protein Cardiac Protein Lysosomotropic Agent 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Amenta, J. S., Sargus, M. J., and Baccino, F. M. 1977. Effect of microtubular or translational inhibitors on general cell protein degradation. Biochem. J. 168:223–227.PubMedGoogle Scholar
  2. 2.
    Ballard, F. J. 1977. Intracellular protein degradation. In: P. N. Campbell and W. N. Aldridge (eds.), Essays in Biochemistry. Vol. 13. pp. 1–37. Academic Press, New York.Google Scholar
  3. 3.
    Barrett, A. J. 1980. The many forms and functions of cellular proteinases. Fed. Proc. Fed. Am. Soc. Exp. Biol. 39:9–14.Google Scholar
  4. 4.
    Crie, J. S., Ord, J. M., Wakeland, J. R., and Wildenthal, K. 1983. Inhibition of cardiac proteolysis by colchicine. Biochem. J. 210:63–71.PubMedGoogle Scholar
  5. 5.
    Dean, R. T. 1980. Regulation and mechanisms of degradation of endogenous proteins by mammalian cells: General considerations. In: K. Wildenthal (ed.), Degradative Processes in Heart and Skeletal Muscle. pp. 3–30. North-Holland, Amsterdam.Google Scholar
  6. 6.
    Grinde, B., and Seglen, P. O. 1981. Role of microtubuli in the lysosomal degradation of endogenous and exogenous protein in isolated rat hepatocytes. Hoppe-Seyler’s Z. Physiol. Chem. 362:549–556.PubMedCrossRefGoogle Scholar
  7. 7.
    Hoh, J. F. Y., McGrath, P. A., and Hale, P. T. 1978. Electrophoretic analysis of multiple forms of rat cardiac myosin: Effects of hypophysectomy and thyroxine replacement. J. Mol. Cell. Cardiol. 10:1053–1076.PubMedCrossRefGoogle Scholar
  8. 8.
    Kolset, S. O., Tolleshaug, H. and Berg, T. 1979. The effects of colchicine and cytochalasin B on uptake and degradation of asialo-glycoproteins in isolated rat hepatocytes. Exp. Cell Res. 122:159–167.PubMedCrossRefGoogle Scholar
  9. 9.
    Libby, P., Ingwall, J. S., and Goldberg, A. L. 1979. Reduction of protein degradation and atrophy in cultured fetal mouse hearts by leupentin. Am. J. Physiol. 237:F35-F39.Google Scholar
  10. 10.
    Ord, J. M., Wakeland, J. R., Crie, J. S., and Wildenthal, K. 1983. Mechanisms of degradation of myofibrillar and nonmyofibrillar protein in heart. In: E. Chazov, V. Saks, and G. Rona (eds.), Advances in Myocardiology. Vol. 4, pp. 195–199. Plenum Press, New York.CrossRefGoogle Scholar
  11. 11.
    Ord, J. M., and Wildenthal, K. 1980. Increased release of δ-aminolevulinic acid from protein during inhibition of protein synthesis in heart: Evidence for the extensive reutilization of heme in cardiac protein metabolism. Biochem. Biophys. Res. Commun. 93:577–582.PubMedCrossRefGoogle Scholar
  12. 12.
    Rannels, D. R., Kao, R., and Morgan, H. E. 1975. Effect of insulin on protein turnover in heart muscle. J. Biol. Chem. 250:1694–1701.PubMedGoogle Scholar
  13. 13.
    Ridout, R. M., Decker, R. S., and Wildenthal, K. 1978. Chloroquine-induced lysosomal abnormalities in cultured foetal mouse hearts. J. Mol. Cell. Cardiol. 10:175–183.PubMedCrossRefGoogle Scholar
  14. 14.
    Seglen, P. O., and Gordon, P. B. 1982. Methyladenine: Specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc. Natl. Acad. Sci. U.S.A. 79:1889–1892.PubMedCrossRefGoogle Scholar
  15. 15.
    Ward, W. F., Chua, B. L., Li, J. B., Morgan, H. E., and Mortimore, G. E. 1979. Inhibition of basal and deprivation-induced proteolysis by leupeptin and pepstatin in perfused rat liver and heart. Biochem. Biophys. Res. Commun. 87:92–98.PubMedCrossRefGoogle Scholar
  16. 16.
    Wibo, M., and Poole, B. 1974. Protein degradation in cultured cells. II. The uptake of chloroquine by rat fibroblasts and the inhibition of cellular protein degradation and cathepsin B1. J. Cell Biol. 63:430–440.PubMedCrossRefGoogle Scholar
  17. 17.
    Wildenthal, K. 1971. Long-term maintenance of spontaneously beating mouse hearts in organ culture. J. Appl. Physiol. 30:153–157.PubMedGoogle Scholar
  18. 18.
    Wildenthal, K., and Crie, J. S. 1980. The role of lysosomes and lysosomal enzymes in cardiac protein turnover. Fed. Proc. Fed. Am. Soc. Exp. Biol. 39:37–41.Google Scholar
  19. 19.
    Wildenthal, K., and Crie, J. S. 1980. Lysosomes and cardiac protein catabolism. In: K. Wildenthal (ed.), Degradative Processes in Heart and Skeletal Muscle. pp. 113–129. North-Holland, Amsterdam.Google Scholar
  20. 20.
    Wildenthal, K., Dees, J. H., and Buja, L. M. 1977. Cardiac lysosomal derangements in mouse heart after long-term exposure to nonmetabolizable sugars Circ. Res. 40:26–35PubMedCrossRefGoogle Scholar
  21. 21.
    Wildenthal, K., Griffin, E. E., and Ingwall, J. S. 1976. Hormonal control of cardiac protein and amino acid balance. Circ. Res. 38(Suppl. 1):138–144.Google Scholar
  22. 22.
    Wildenthal, K., Wakeland, J. R., Morton, P. C., and Griffin, E. E. 1978. Inhibition of protein degradation in mouse hearts by agents that cause lysosomal dysfunction. Circ. Res. 42:787–792.PubMedCrossRefGoogle Scholar
  23. 23.
    Wildenthal, K., Wakeland, J. R., Ord, J. M., and Stull, J. T. 1980. Interference with lysosomal proteolysis fails to reduce cardiac myosin degradation. Biochem. Biophys. Res. Commun. 96:793–798.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • K. Wildenthal
    • 1
  • J. S. Crie
    • 1
  • J. M. Ord
    • 1
  • J. R. Wakeland
    • 1
  1. 1.Pauline and Adolph Weinberger Laboratory for Cardiopulmonary Research, Departments of Physiology and Internal MedicineThe University of Texas Health Science Center at DallasDallasUSA

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