Linked Life Data

19804812

Source:http://linkedlifedata.com/resource/pubmed/id/19804812

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2010-2-1
pubmed:abstractText
Very little is known about the signaling pathways by which catecholamines exert anabolic effects on muscle protein metabolism, stimulating protein synthesis and suppressing proteolysis. The present work tested the hypothesis that epinephrine-induced inhibition of muscle proteolysis is mediated through the cAMP/Epac/PI3K-dependent pathway with the involvement of AKT and Foxo. The incubation of extensor digitorum longus (EDL) muscles from rats with epinephrine and/or insulin increased the phosphorylation of AKT and its downstream target Foxo3a, a well-known effect that prevents Foxo translocation to the nucleus and the activation of proteolysis. Similar effects on AKT/Foxo signaling were observed in muscles incubated with DBcAMP (cAMP analog). The stimulatory effect of epinephrine on AKT phosphorylation was completely blocked by wortmannin (selective PI3K inhibitor), suggesting that the epinephrine-induced activation of AKT is mediated through PI3K. As for epinephrine and DBcAMP, the incubation of muscles with 8CPT-2Me-cAMP (selective Epac agonist) reduced rates of proteolysis and increased phosphorylation levels of AKT and Foxo3a. The specific PKA agonist (N6BZ-cAMP) inhibited proteolysis and abolished the epinephrine-induced AKT and Foxo3a phosphorylation. On the other hand, inhibition of PKA by H89 further increased the phosphorylation levels of AKT and Foxo3a induced by epinephrine, DBcAMP or 8CPT-2Me-cAMP. These findings suggest that the antiproteolytic effect of the epinephrine on isolated skeletal muscle may occur through a cAMP/Epac/PI3K-dependent pathway, which leads to the phosphorylation of AKT and Foxo3a. The parallel activation of PKA-dependent pathway also inhibits proteolysis and seems to limit the stimulatory effect of cAMP on AKT/Foxo3a signaling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Androstadienes, http://linkedlifedata.com/resource/pubmed/chemical/Bucladesine, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP, http://linkedlifedata.com/resource/pubmed/chemical/Epac-1 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Epinephrine, http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Foxo3a protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Guanine Nucleotide Exchange Factors, http://linkedlifedata.com/resource/pubmed/chemical/Insulin, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleosides, http://linkedlifedata.com/resource/pubmed/chemical/triciribine, http://linkedlifedata.com/resource/pubmed/chemical/wortmannin
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1872-8057
pubmed:author
pubmed:copyrightInfo
2009 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
5
pubmed:volume
315
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
104-12
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Involvement of cAMP/Epac/PI3K-dependent pathway in the antiproteolytic effect of epinephrine on rat skeletal muscle.
pubmed:affiliation
Department of Chemistry, Federal University of Mato Grosso, 78060-900 Cuiabá, MT, Brazil.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't