|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
5
|
|
pubmed:dateCreated |
2005-9-5
|
|
pubmed:abstractText |
Metabolic abnormalities develop in various chronic diseases and lead to progressive catabolism with decrements in the skeletal musculature that result in muscle atrophy. We investigated pathways of skeletal muscle proteolysis using an experimental model of chronic left-ventricular dysfunction. Skeletal muscle atrophy developed in wild-type mice 12 weeks following myocardial infarction accompanied by an increase in total protein ubiquitination and enhanced proteasome activity, activation of Foxo transcription factors, and robust induction of the ubiquitin-protein ligase atrogin-1/MAFbx. Further studies identified skeletal muscle myosin as a specific target of ubiquitin-mediated degradation in muscle atrophy. In contrast, transgenic overexpression of a local isoform of insulin-like growth factor-1 prevented muscle atrophy and increased proteasome activity, inhibited skeletal muscle activation primarily of Foxo4, and blocked the expression of atrogin-1/MAFbx. These results suggest that skeletal muscle atrophy occurs through increased activity of the ubiquitin-proteasome pathway. The inhibition of muscle atrophy by local insulin-like growth factor-1 provides a promising therapeutic avenue for the prevention of skeletal muscle wasting in chronic heart failure and potentially other chronic diseases associated with skeletal muscle atrophy.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATP dependent 26S protease,
http://linkedlifedata.com/resource/pubmed/chemical/Fbxo32 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Foxo1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myosin Light Chains,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/SKP Cullin F-Box Protein Ligases,
http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/mTOR protein, mouse
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Sep
|
|
pubmed:issn |
1524-4571
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
2
|
|
pubmed:volume |
97
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
418-26
|
|
pubmed:dateRevised |
2010-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:16051886-Animals,
pubmed-meshheading:16051886-Cells, Cultured,
pubmed-meshheading:16051886-Chronic Disease,
pubmed-meshheading:16051886-Forkhead Transcription Factors,
pubmed-meshheading:16051886-Insulin-Like Growth Factor I,
pubmed-meshheading:16051886-Male,
pubmed-meshheading:16051886-Mice,
pubmed-meshheading:16051886-Mice, Transgenic,
pubmed-meshheading:16051886-Muscle, Skeletal,
pubmed-meshheading:16051886-Muscle Proteins,
pubmed-meshheading:16051886-Muscular Atrophy,
pubmed-meshheading:16051886-Myocardial Infarction,
pubmed-meshheading:16051886-Myosin Light Chains,
pubmed-meshheading:16051886-Proteasome Endopeptidase Complex,
pubmed-meshheading:16051886-Protein Kinases,
pubmed-meshheading:16051886-Protein-Serine-Threonine Kinases,
pubmed-meshheading:16051886-Proto-Oncogene Proteins,
pubmed-meshheading:16051886-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:16051886-SKP Cullin F-Box Protein Ligases,
pubmed-meshheading:16051886-Signal Transduction,
pubmed-meshheading:16051886-TOR Serine-Threonine Kinases,
pubmed-meshheading:16051886-Transcription Factors,
pubmed-meshheading:16051886-Ubiquitin,
pubmed-meshheading:16051886-Ventricular Dysfunction, Left
|
|
pubmed:year |
2005
|
|
pubmed:articleTitle |
Transgenic overexpression of locally acting insulin-like growth factor-1 inhibits ubiquitin-mediated muscle atrophy in chronic left-ventricular dysfunction.
|
|
pubmed:affiliation |
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. christian.schulze@bmc.org
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
