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Two-step mechanism of myofibrillar protein degradation in acute plasmocid-induced muscle necrosis.

Abstract
Acute muscle necrosis was induced in rats by intramuscular injection of plasmocid, a known myotoxic agent. A single injection of 5 mg/ml plasmocid produced massive fiber necrosis with extensive phagocytosis. Plasmocid administration led to a preferential decrease of alpha-actinin with preservation of other structural proteins within 3 h after injection, and large increases (2-7-fold) in the activities of acid hydrolases, cathepsins B and L, cathepsin D and alpha-galactosidase within 48 h after injection. The plasmocid-induced stimulation of alpha-actinin loss seen at 3 h, when no increases of acid hydrolases occurred, could be inhibited by a cysteine protease inhibitor, Ep-475 (E-64-c), and EGTA. On the other hand, increased lysosomal enzyme activity seemed to have a close correlation with the appearance of invading mononuclear cells, probably macrophages, and not muscle lysosomes. These observations suggest that a two step mechanism of protein degradation (nonlysosomal and lysosomal processes) possibly occurs in plasmocid-induced muscle degradation and macrophages can serve as a main endogenous reservoir of proteases in pathological states.
AuthorsS Ishiura, I Nonaka, H Nakase, A Tada, H Sugita
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 798 Issue 3 Pg. 333-42 (Apr 24 1984) ISSN: 0006-3002 [Print] Netherlands
PMID6424726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Aminoquinolines
  • Muscle Proteins
  • Protease Inhibitors
  • Actinin
  • Egtazic Acid
  • N-(N-(3-carboxyoxirane-2-carbonyl)leucyl)isoamylamine
  • pamaquine
  • Leucine
Topics
  • Actinin (metabolism)
  • Aminoquinolines (toxicity)
  • Animals
  • Egtazic Acid (pharmacology)
  • Leucine (analogs & derivatives, pharmacology)
  • Lysosomes (enzymology)
  • Male
  • Muscle Proteins (metabolism)
  • Muscles (drug effects, pathology)
  • Necrosis
  • Phagocytosis (drug effects)
  • Protease Inhibitors (pharmacology)
  • Rats
  • Rats, Inbred Strains

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