COMPARISON OF STRUCTURAL PROTEIN AND PROTEOLYTIC-ENZYME LEVELS IN DEGENERATING AND REGENERATING RAT MUSCLE INDUCED BY NOTECHIS-SCUTATUS VENOM

To develop a clearer understanding of the biochemical mechanism of mus cle 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 de gradation of structural proteins post-injection fell into two broad gr oups; those completely degraded within 3-6 hr (e.g. C- and M-proteins, skelemin), and within 1-2 days (e.g. myosin, actin, troponin), respec tively. Similarly, activation of proteases followed two general patter ns; those enzymes showing substantially increased activity after 12-24 hr (lysosomal cathepsins, leucyl aminopeptidase) and those enzymes sh owing decreased activity after 12-24 hr, with substantially increased activity after 3-4 days (mainly cytoplasmic proteases). The data sugge st that activation of cathepsins B, L and D and in particular leucyl a minopeptidase, may be responsible for the early stages of structural p rotein catabolism, and are thus potential therapeutic targets to preve nt myonecrosis following envenomation.