Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1980 Feb;98(2):445–456.

Lysosomal alterations in hypoxic and reoxygenated hearts. II. Immunohistochemical and biochemical changes in cathepsin D.

R S Decker, A R Poole, J S Crie, J T Dingle, K Wildenthal
PMCID: PMC1903426  PMID: 6986784

Abstract

Sublethal hypoxic injury in rat and rabbit hearts was accompanied by a biochemical redistribution of cathepsin D activity from the particulate to the supernatant fraction of the tissue homogenate, which was partially reversible on reoxygenation. Immunofluorescent staining for cathepsin D failed to reveal major anatomic release of the acid hydrolase until necrosis was present, suggesting that the earlier biochemical redistribution was primarily a result of increased lysosomal fragility during homogenization, with significant intracellular diffusion of the enzyme occurring only as irreversible damage took place. Hypoxia produced enlargement of both cathepsin-D-staining lysosomes and nonstaining vacuoles, as well as their aggregation. These changes were intensified during reoxygenation and recovery of reversibly damaged hearts, suggesting a possible role for the lysosomal-vacuolar apparatus in myocytic repair following hypoxic injury.

Full text

PDF
445

Images in this article

Selected References

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

  1. Decher R. S., Poole A. R., Dingle J. T., Wildenthal K. Influence of methylprednisolone of the sequential redistribution of cathepsin D and other lysosomal enzymes during myocardial ischemia in rabbits. J Clin Invest. 1978 Oct;62(4):797–804. doi: 10.1172/JCI109191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Decker R. S., Poole A. R., Dingle J. T., Wildenthal K. Lysosomal alterations in autolyzing rabbit heart. J Mol Cell Cardiol. 1979 Feb;11(2):189–196. doi: 10.1016/0022-2828(79)90463-2. [DOI] [PubMed] [Google Scholar]
  3. Decker R. S., Poole A. R., Griffin E. E., Dingle J. T., Wildenthal K. Altered distribution of lysosomal cathepsin D in ischemic myocardium. J Clin Invest. 1977 May;59(5):911–921. doi: 10.1172/JCI108713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Decker R. S., Wildenthal K. Lysosomal alterations in hypoxic and reoxygenated hearts. I. Ultrastructural and cytochemical changes. Am J Pathol. 1980 Feb;98(2):425–444. [PMC free article] [PubMed] [Google Scholar]
  5. Decker R. S., Wildenthal K. Sequential lysosomal alterations during cardiac ischemia. II. Ultrastructural and cytochemical changes. Lab Invest. 1978 Jun;38(6):662–673. [PubMed] [Google Scholar]
  6. Ganote C. E., Seabra-Gomes R., Nayler W. G., Jennings R. B. Irreversible myocardial injury in anoxic perfused rat hearts. Am J Pathol. 1975 Sep;80(3):419–450. [PMC free article] [PubMed] [Google Scholar]
  7. HERDSON P. B., SOMMERS H. M., JENNINGS R. B. A COMPARATIVE STUDY OF THE FINE STRUCTURE OF NORMAL AND ISCHEMIC DOG MYOCARDIUM WITH SPECIAL REFERENCE TO EARLY CHANGES FOLLOWING TEMPORARY OCCLUSION OF A CORONARY ARTERY. Am J Pathol. 1965 Mar;46:367–386. [PMC free article] [PubMed] [Google Scholar]
  8. Hoffstein S., Gennaro D. E., Weissmann G., Hirsch J., Streuli F., Fox A. C. Cytochemical localization of lysosomal enzyme activity in normal and ischemic dog myocardium. Am J Pathol. 1975 May;79(2):193–206. [PMC free article] [PubMed] [Google Scholar]
  9. Ingwall J. S., DeLuca M., Sybers H. D., Wildenthal K. Fetal mouse hearts: a model for studying ischemia. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2809–2813. doi: 10.1073/pnas.72.7.2809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kloner R. A., Ganote C. E., Whalen D. A., Jr, Jennings R. B. Effect of a transient period of ischemia on myocardial cells. II. Fine structure during the first few minutes of reflow. Am J Pathol. 1974 Mar;74(3):399–422. [PMC free article] [PubMed] [Google Scholar]
  11. MORGAN H. E., HENDERSON M. J., REGEN D. M., PARK C. R. Regulation of glucose uptake in muscle. I. The effects of insulin and anoxia on glucose transport and phosphorylation in the isolated, perfused heart of normal rats. J Biol Chem. 1961 Feb;236:253–261. [PubMed] [Google Scholar]
  12. McCallister L. P., Munger B. L., Neely J. R. Electron microscopic observations and acid phosphatase activity in the ischemic rat heart. J Mol Cell Cardiol. 1977 May;9(5):353–364. doi: 10.1016/s0022-2828(77)80002-3. [DOI] [PubMed] [Google Scholar]
  13. Nayler W. G., Yepez C., Grau A., Slade A. Protective effect of methylprednisolone sodium succinate on the ultrastructure and resting tension of hypoxic heart muscle. Cardiovasc Res. 1978 Feb;12(2):91–98. doi: 10.1093/cvr/12.2.91. [DOI] [PubMed] [Google Scholar]
  14. Welman E., Peters T. J. Enhanced lysosome fragility in the anoxic perfused guinea pig heart: effects of glucose and mannitol. J Mol Cell Cardiol. 1977 Feb;9(2):101–120. doi: 10.1016/0022-2828(77)90043-8. [DOI] [PubMed] [Google Scholar]
  15. Wildenthal K., Decker R. S., Poole A. R., Dingle J. T. Age-related alterations in cardiac lysosomes. J Mol Cell Cardiol. 1977 Oct;9(10):859–866. doi: 10.1016/s0022-2828(77)80062-x. [DOI] [PubMed] [Google Scholar]
  16. Wildenthal K., Decker R. S., Poole A. R., Griffin E. E., Dingle J. T. Sequential lysosomal alterations during cardiac ischemia. I. Biochemical and immunohistochemical changes. Lab Invest. 1978 Jun;38(6):656–661. [PubMed] [Google Scholar]
  17. Wildenthal K. Lysosomal alterations in ischemic myocardium: result or cause of myocellular damage? J Mol Cell Cardiol. 1978 Jul;10(7):595–603. doi: 10.1016/s0022-2828(78)80001-7. [DOI] [PubMed] [Google Scholar]
  18. Wildenthal K., Poole A. R., Dingle J. T. Influence of starvation on the activities and localization of cathepsin D and other lysosomal enzymes in hearts of rabbits and mice. J Mol Cell Cardiol. 1975 Nov;7(11):841–855. doi: 10.1016/0022-2828(75)90135-2. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES