NASA Logo

NTRS

NTRS - NASA Technical Reports Server

Back to Results
Patterns of gene expression in atrophying skeletal muscles: response to food deprivationDuring 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.
Document ID
20040088013
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Jagoe, R. Thomas
(Harvard Medical School Boston, Massachusetts, United States)
Lecker, Stewart H.
Gomes, Marcelo
Goldberg, Alfred L.
Date Acquired
August 21, 2013
Publication Date
November 1, 2002
Publication Information
Publication: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume: 16
Issue: 13
ISSN: 0892-6638
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: DK02707
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Musculoskeletal

Available Downloads

There are no available downloads for this record.
No Preview Available