title: 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.
mesh_terms: D000185:Actinin / Q000378:metabolism; D000634:Aminoquinolines / Q000633:toxicity*; D000818:Animals; D004533:Egtazic Acid / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000473:pathology*; D009336:Necrosis; D010587:Phagocytosis / Q000187:drug effects; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000634:Aminoquinolines; D009124:Muscle Proteins; D011480:Protease Inhibitors; D000185:Actinin; D004533:Egtazic Acid; C032425:N-(N-(3-carboxyoxirane-2-carbonyl)leucyl)isoamylamine; C004331:pamaquine; D007930:Leucine