Patterns of gene expression in atrophying skeletal muscles: response to food deprivation

Male 2. Zero hunger 0301 basic medicine 0303 health sciences Gene Expression Profiling Body Weight Apoptosis Carbonic Anhydrase III Electron Transport Mice, Inbred C57BL Mice 03 medical and health sciences Gene Expression Regulation Glutamate-Ammonia Ligase Endopeptidases Animals Atrophy Food Deprivation Insulin-Like Growth Factor Binding Protein 5 Muscle, Skeletal Creatine Kinase Glycolysis Cell Division Oligonucleotide Array Sequence Analysis
DOI: 10.1096/fj.02-0312com Publication Date: 2002-10-30T18:44:20Z
ABSTRACT
During fasting and many systemic diseases, muscle undergoes rapid loss of protein and functional capacity. To define the transcriptional changes triggering muscle atrophy and energy conservation in fasting, we used cDNA microarrays to compare mRNAs from muscles of control and food‐deprived mice. Expression of >94% of genes did not change, but interesting patterns emerged among genes that were differentially expressed: 1) mRNAs encoding polyubiquitin, ubiquitin extension proteins, and many (but not all) proteasome subunits increased, which presumably contributes to accelerated protein breakdown; 2) a dramatic increase in mRNA for the ubiquitin ligase, atrogin‐1, but not most E3s; 3) a significant suppression of mRNA for myosin binding protein H (but not other myofibrillar proteins) and IGF binding protein 5, which may favor cell protein loss; 4) decreases in mRNAs for several glycolytic enzymes and phosphorylase kinase subunits, and dramatic increases in mRNAs for pyruvate dehydrogenase kinase 4 and glutamine synthase, which should promote glucose sparing and gluconeogenesis. During fasting, metallothionein mRNA increased dramatically, mRNAs for extracellular matrix components fell, and mRNAs that may favor cap‐independent mRNA translation rose. Significant changes occurred in mRNAs for many growth‐related proteins and transcriptional regulators. These transcriptional changes indicate a complex adaptive program that should favor protein degradation and suppress glucose oxidation in muscle. Similar analysis of muscles atrophying for other causes is allowing us to identify a set of atrophy‐specific changes in gene expression.—Jagoe, R. T., Lecker, S. H., Gomes, M., Goldberg, A. L. Patterns of gene expression in atrophying skeletal muscles: response to food deprivation. FASEB J. 16, 1697–1712 (2002)
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