Linked Life Data

19696026

Source:http://linkedlifedata.com/resource/pubmed/id/19696026

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
41
pubmed:dateCreated
2009-10-5
pubmed:abstractText
In the heart, autophagy is required for normal cardiac function and also has been implicated in cardiovascular disease. FoxO transcription factors promote autophagy in skeletal muscle and have additional roles in regulation of cell size, proliferation, and metabolism. Here we investigate the role of FoxO transcription factors in regulating autophagy and cell size in cardiomyocytes. In cultured rat neonatal cardiomyocytes, glucose deprivation leads to decreased cell size and induction of autophagy pathway genes LC3, Gabarapl1, and Atg12. Likewise, overexpression of either FoxO1 or FoxO3 reduces cardiomyocyte cell size and induces expression of autophagy pathway genes. Moreover, inhibition of FoxO activity by dominant negative FoxO1 (Delta256) blocks cardiomyocyte cell size reduction upon starvation, suggesting the necessity of FoxO function in cardiomyocyte cell size regulation. Under starvation conditions, endogenous FoxO1 and FoxO3 are localized to the nucleus and bind to promoter sequences of Gabarapl1 and Atg12. In vivo studies show that cellular stress, such as starvation or ischemia/reperfusion in mice, results in induction of autophagy in the heart with concomitant dephosphorylation of FoxO, consistent with increased activity of nuclear FoxO transcription factors. Together these results provide evidence for an important role for FoxO1 and FoxO3 in regulating autophagy and cell size in cardiomyocytes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Apg12l protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Foxo1 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Foxo3a protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Gabarapl2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/MAP1LC3 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proteins
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28319-31
pubmed:dateRevised
2010-10-12
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
FoxO transcription factors promote autophagy in cardiomyocytes.
pubmed:affiliation
Division of Molecular Cardiovascular Biology, Cincinnati Children's Medical Center, Cincinnati, Ohio 45229, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural