Influence of methylprednisolone on the sequential redistribution of cathepsin D and other lysosomal enzymes during myocardial ischemia in rabbits

R. S. Decker, A. R. Poole, J. T. Dingle, K. Wildenthal

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Occlusion of the circumflex coronary artery induced a profound redistribution in ischemic rabbit myocardium of several lysosomal acid hydrolases, including cathepsin D, B-acetylglucosaminidase, and acid phosphatase. 30-45 min after ligation non-sedimentable cathepsin D activity rose from 36% of the total activity to 42-48% and in immunohistochemical preparations cathepsin D appeared to have diffused from lysosomes into the cytosol of injured cells. A pharmacologic dose of methylprednisolone (50 mg/kg) significantly delayed the subcellular redistribution of cathepsin D and the other hydrolases in ischemic heart. Thus, in treated hearts the nonsedimentable activity of cathepsin D rose to only 38% after 30 min of ischemia and 42% after 45 min (P<0.05 compared to untreated ischemia at each time). Similarly, unlike untreated hearts, no evidence of enzyme diffusion from lysosomes could be demonstrated immunohistochemically in corticosteroid-treated ischemic hearts for over 45 min. After 1-2 h of ischemia, however, steroid-protected myocytes deteriorated and the biochemical activity and anatomical distribution of cathepsin D were indistinguishable from untreated ischemic hearts. This study demonstrates that corticosteroid pretreatment does not prevent alterations in cardiac lysosomes during severe ischemia indefinitely, but does delay their development significantly.

Original languageEnglish (US)
Pages (from-to)797-804
Number of pages8
JournalJournal of Clinical Investigation
Volume62
Issue number4
DOIs
StatePublished - Jan 1 1978

ASJC Scopus subject areas

  • Medicine(all)

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