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.
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Authors | S Ishiura, I Nonaka, H Nakase, A Tada, H Sugita |
Journal | Biochimica et biophysica acta
(Biochim Biophys Acta)
Vol. 798
Issue 3
Pg. 333-42
(Apr 24 1984)
ISSN: 0006-3002 [Print] Netherlands |
PMID | 6424726
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Aminoquinolines
- Muscle Proteins
- Protease Inhibitors
- Actinin
- Egtazic Acid
- N-(N-(3-carboxyoxirane-2-carbonyl)leucyl)isoamylamine
- pamaquine
- Leucine
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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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