Comparison of structural protein and proteolytic enzyme levels in degenerating and regenerating rat muscle induced by Notechis scutatus venom.
To develop a clear understanding of the biochemical mechanism of muscle degeneration and regeneration induced by a single dose of Notechis scutatus scutatus venom, we have correlated changes in the levels of a series of muscle structural proteins and proteolytic enzymes. The degradation of structural proteins post-injection fell into two broad groups; those completely degraded within 3-6 hr (e.g. C- and M-proteins, skelemin), and within 1-2 days (e.g. myosin, actin, troponin), respectively. Similarly, activation of proteases followed two general patterns; those enzymes showing substantially increased activity after 12-24 hr (lysosomal cathepsins, leucyl aminopeptidase) and those enzymes showing decreased activity after 12-24 hr, with substantially increased activity after 3-4 days (mainly cytoplasmic proteases). The data suggest that activation of cathepsins B, L and D and in particular leucyl aminopeptidase, may be responsible for the early stages of structural protein catabolism, and are thus potential therapeutic targets to prevent myonecrosis following envenomation.
Abul Faiz
M
M
Muscular Dystrophy Group Research Laboratories, Newcastle General Hospital, U.K.
Harris
J B
JB
Maltin
C A
CA
Mantle
D
D
D000199:Actins / Q000378:metabolism; D000818:Animals; D002403:Cathepsins / Q000378:metabolism; D064211:Connectin; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004546:Elapid Venoms / Q000494:pharmacology*; D010450:Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D007700:Kinetics; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000502:physiology*; D009194:Myeloma Proteins; D009218:Myosins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D014336:Troponin / Q000378:metabolism
D000199:Actins; D064211:Connectin; D003598:Cytoskeletal Proteins; D004546:Elapid Venoms; D009124:Muscle Proteins; D009194:Myeloma Proteins; D014336:Troponin; C085016:multiple myeloma M-proteins; D002403:Cathepsins; D010450:Endopeptidases; D007931:Leucyl Aminopeptidase; D009218:Myosins