Plasminogen activator in XXXX skeletal muscle: characteristics of effect of denervation on urokinase-like and tissue activator.

@entity19 @entity1 @entity5 @entity4094
Analyses were made of the fibrinolytic, plasminogen-activating system in skeletal muscle to determine if a regulating influence of the nerve could be detected on these enzymes. Young male @entity19 underwent right sciatic neurectomy. Extracts were prepared from denervated muscle at 2-17 d after axotomy and compared with controls. Using a cascade-style biochemical assay (R  nby, M., B. Norrman, and P. Wall  n, 1982, Thromb. Res., 27:743-748) we found that low levels of plasminogen activator (PA) were present in adult, innervated @entity19 muscle, but that denervation resulted in a marked time-dependent increase in enzyme activity. Qualitative separation showed an eightfold increase in urokinase-like PA with moderate elevation of tissue PA activity after 10 d. Fibrin zymography (Granelli-Piperno, A., and E. Reich, 1978, J. Exp. Med., 148:223-234) revealed clear zones of lysis corresponding to molecular masses of 48 kD for urokinase-like PA and 75 kD for tissue PA, consistent with the molecular masses found for these enzymes in other tissues of the @entity19 (Dan  , K., P. A. Andreasen, J. Gr  ndahl-Hansen, P. Kristensen, L. S. Nielsen, and L. Skriver, 1985, Adv. @entity5 Res., 44:139-266). In other studies we have shown that PA-activated plasmin readily attacks critical adhesive basement membrane molecules. The present results indicate that enzymes involved in plasminogen activation, particularly urokinase-like PA, rapidly increase after axotomy, suggesting they may have a role early in muscle denervation. Similar alterations in PA activity might underlie the elimination of polyneuronal innervation during @entity1 muscle development. Certain @entity4094 may also involve activation of these enzymes, resulting in degradation of basement membrane zone components and, therefore, warrant further study.
