Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-7-10
pubmed:abstractText
beta -adrenergic agonists stimulate neonatal rat cardiac fibroblast growth, albeit the identity of the signaling event(s) remains equivocal. Isoproterenol (ISO) treatment increased intracellular cyclic AMP levels; however, cyclic AMP-elevating agents had no effect on protein synthesis. The tyrosine kinase inhibitor tyrphostin A25, and the inhibition of ras processing by the farnesyltransferase inhibitor BMS-191563 attenuated ISO-stimulated protein synthesis. Concomitant with increased protein synthesis, ISO stimulated extracellular signal-regulated protein kinase (ERK) and phosphatidylinositol 3-kinase (PI3-K) activity. The MEK1/2 inhibitor PD098059 abrogated ISO-stimulated ERK activity, albeit the increase in protein synthesis was unaffected. By contrast, LY294002 inhibited both ISO-stimulated PI3-K activity, and protein synthesis. ISO treatment did not increase the expression of transforming growth factor-beta(1)(TGF-beta(1)) mRNA, whereas a significant decrease in the steady-state mRNA level of TGF- beta(3)was observed. This latter effect was mimicked by cyclic AMP-elevating agents. Angiotensin II (AII) activation of the AT(1)receptor increased protein synthesis, but in contrast to ISO, the growth response was not inhibited by either tyrphostin A25 or BMS-191563, and was associated with the concomitant expression of both TGF-beta(1)and TGF-beta(3)mRNAs. Analogous to ISO, AII treatment increased ERK and PI3-K activity, and PI3-K was required for protein synthesis. These findings are the first to highlight the activation of PI3-K by a Gs(alpha)-coupled receptor, and its essential role in beta -adrenergic as well as AT(1)receptor-mediated protein synthesis in neonatal rat cardiac fibroblasts. However, despite the conserved role of PI3-K, additional disparate signaling pathways are recruited by ISO and AII, which may differentially influence fibroblast phenotype.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta-2, http://linkedlifedata.com/resource/pubmed/chemical/Tgfb1 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Tgfb3 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta2, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta3, http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins, http://linkedlifedata.com/resource/pubmed/chemical/tyrphostin 25
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2828
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1091-106
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:11444915-Adrenergic beta-Agonists, pubmed-meshheading:11444915-Angiotensin II, pubmed-meshheading:11444915-Animals, pubmed-meshheading:11444915-Cell Division, pubmed-meshheading:11444915-Cells, Cultured, pubmed-meshheading:11444915-Cyclic AMP, pubmed-meshheading:11444915-Enzyme Activation, pubmed-meshheading:11444915-Enzyme Inhibitors, pubmed-meshheading:11444915-Fibroblasts, pubmed-meshheading:11444915-Isoproterenol, pubmed-meshheading:11444915-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:11444915-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:11444915-Mitogen-Activated Protein Kinases, pubmed-meshheading:11444915-Myocardium, pubmed-meshheading:11444915-Phosphatidylinositol 3-Kinases, pubmed-meshheading:11444915-Protein Biosynthesis, pubmed-meshheading:11444915-Protein-Tyrosine Kinases, pubmed-meshheading:11444915-Rats, pubmed-meshheading:11444915-Rats, Sprague-Dawley, pubmed-meshheading:11444915-Receptors, Adrenergic, beta-2, pubmed-meshheading:11444915-Signal Transduction, pubmed-meshheading:11444915-Transforming Growth Factor beta, pubmed-meshheading:11444915-Transforming Growth Factor beta1, pubmed-meshheading:11444915-Transforming Growth Factor beta2, pubmed-meshheading:11444915-Transforming Growth Factor beta3, pubmed-meshheading:11444915-Tyrphostins
pubmed:year
2001
pubmed:articleTitle
beta-Adrenergic stimulation of rat cardiac fibroblasts promotes protein synthesis via the activation of phosphatidylinositol 3-kinase.
pubmed:affiliation
Departément de Physiologie, Université de Montréal, Montréal, Québec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't