ANALYSIS OF EVENTS ASSOCIATED WITH SERUM DEPRIVATION-INDUCED APOPTOSIS IN C3H SOL8 MUSCLE SATELLITE CELLS/

Satellite cells are the source of new muscle fibers in postnatal skele tal muscle growth and regeneration. Regulation of satellite cell survi val is of fundamental importance in maintaining normal muscle function . Here we describe and characterize a tissue culture model of satellit e cell apoptosis. Kinetic studies indicate that serum deprivation trig gers a set of sequential events: early cell death, transient cell cycl e traverse, and delayed cell death. The satellite cell death occurs by apoptosis based on the internucleosomal DNA laddering, in situ DNA en d-labeling, and the requirements for de novo protein synthesis and ext racellular calcium influx. The transient period of cell cycle progress ion (7-11 h after serum withdrawal) is accompanied by temporal inducti on of members of the immediate early gene family, such as c-myc, c-fos , and SRF, and appears to precede the delayed phase of cell death. Sat ellite cell apoptosis can be suppressed by several growth factors and by blocking the activity of calpain, a calcium-regulated protease. The late phase of apoptosis is marked by selective activation of ubiquiti n-mediated protein conjugation and degradation. This study defines sev eral control points where satellite cell apoptosis may be genetically or pharmacologically intervened. (C) 1996 Academic Press, Inc.