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.
Muscular Dystrophy Group Research Laboratories, Newcastle General Hospital, U.K.
M
M
Abul Faiz
J B
JB
Harris
C A
CA
Maltin
D
D
Mantle
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