Skeletal muscle wasting is a pervasive phenomenon that can result from a wide range of pathological conditions as well as from habitual muscular inactivity. The present work describes a cell-culture condition that induces significant
atrophy in skeletal muscle C2C12 myotubes. The failure to replenish differentiation media in mature myotubes leads to rapid
atrophy (53% in diameter), which is referred to here as
starvation. Affymetrix microarrays were used to develop a transcriptional profile of control (fed) vs. atrophied (nonfed) myotubes. Myotube
starvation was characterized by an upregulation of genes involved in translational inhibition,
amino acid biosynthesis and transport, and cell cycle arrest/apoptosis, among others. Downregulated genes included several structural and regulatory elements of the extracellular matrix as well as several elements of Wnt/frizzled and
TGF-beta signaling pathways. Interestingly, the characteristic transcriptional upregulation of the
ubiquitin-
proteasome system, calpains, and
cathepsins known to occur in multiple in vivo models of
atrophy were not seen during myotube
starvation. With the exception of the downregulation of extracellular matrix genes,
serine protease inhibitor genes, and the upregulation of the translation
initiation factor PHAS-I, this model of
atrophy in cell culture has a transcriptional profile quite distinct from any study published to date with
atrophy in whole muscle. These data show that, although the gross morphology of atrophied muscle fibers may be similar in whole muscle vs. myotube culture, the processes by which this phenotype is achieved differ markedly.