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Protease nexin I, a serpin, inhibits plasminogen‐dependent degradation of muscle extracellular matrix
Author(s) -
Rao J. S.,
Kahler C. B.,
Baker J. B.,
Festoff B. W.
Publication year - 1989
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.880120805
Subject(s) - biochemistry , protease , plasmin , plasminogen activator , extracellular matrix , chemistry , myogenesis , serpin , serine protease , extracellular , microbiology and biotechnology , biology , in vitro , enzyme , endocrinology , gene
Clonal, fusing, mouse skeletal muscle cells (C2) were grown to the myotube stage (90% confluence) before they were subjected to isotope containing serum‐free media ( 3 H‐proline or 35 S‐methionine). C2 myotubes secrete and organize a biosynthetically labeled matrix which adheres to the plastic after removal of myotubes with detergent and ammonium hydroxide. When these homotypic‐labeled myotube matrices were incubated with myo blast‐conditioned media containing high specific activity urokinase‐type plasminogen activator, slow, but clearly detectable, release of label occurred. However, degradation of matrix, with solubilization of label, was accelerated sixfold by addition of human plasminogen to diluted myoblast conditioned media. If protease nexin I, a cellular serine protease inhibitor purified from human fibroblast‐conditioned media, was added (0.2 μg/ml) with plasminogen, inhibition of matrix hydrolysis by 52% occurred. Higher concentrations (0.8 μg/ml or above) of protease nexin I completely inhibited the degradation of extracellular matrix components. A similar protease inhibitor was purified from C2 myotube‐conditioned media, and this molecule also inhibited the plasminogen‐dependent release of extracellular matrix. We propose that protease nexin I inhibits the destruction of myotube matrix by inactivating the plasmin/plasminogen activation system and may be the physiologic regulator of this system during muscle development in vivo.