rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2007-3-12
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pubmed:abstractText |
Beta-adrenergic receptor (beta-AR) stimulation induces apoptosis in adult rat ventricular myocytes (ARVM). beta1 integrin signaling plays a protective role in beta-AR-stimulated apoptosis. Glycogen synthase kinase-3beta (GSK-3beta), a multifunctional serine/threonine kinase, negatively regulates cardiac hypertrophy. Here we show that beta-AR stimulation (isoproterenol; 15 min) increases tyr(216) phosphorylation and GSK-3beta activity. Inclusion of LiCl, inhibitor of GSK-3beta, in the reaction mix or expression of catalytically inactive GSK-3beta (KM-GSK) inhibited beta-AR-stimulated GSK-3beta activity. Inhibition of tyrosine kinase using genistein or chelation of intracellular Ca(2+) using BAPTA-AM inhibited beta-AR-stimulated increases in tyr(216) phosphorylation and GSK-3beta activity. Inhibition of GSK-3beta using pharmacological inhibitors or infection with KM-GSK decreased beta-AR-stimulated cytosolic cytochrome C release and apoptosis. Expression of beta1 integrins increased ser(9) phosphorylation and inhibited beta-AR-stimulated increase in GSK-3beta activity. Wortmannin, inhibitor of PI3-kinase, reversed the effects of beta1 integrins on GSK-3beta activity and apoptosis. Purified active matrix metalloproteinase-2 (MMP-2), shown to interfere with beta1 integrin signaling, increased GSK-3beta activity, while inhibition of MMP-2 inhibited beta-AR-stimulated increases in GSK-3beta activity. beta-AR stimulation induced nuclear accumulation of GSK-3beta. beta-AR stimulation (3 h) increased the expression of transcription factor Gadd153 (growth arrest- and DNA damage-inducible gene 153). These data suggest that beta-AR stimulation increases GSK-3beta activity. Activation of GSK-3beta plays a pro-apoptotic role in beta-AR-stimulated apoptosis via the involvement of mitochondrial death pathway. beta1 integrins inactivate GSK-3beta and play an anti-apoptotic role via the involvement of PI3-kinase pathway. The apoptotic effects of GSK-3beta may be mediated, at least in part, via its nuclear localization and induction of pro-apoptotic genes, such as Gadd153.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17292911-10687952,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17292911-11018058,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17292911-11094086,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17292911-11158311,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17292911-11748583,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17292911-9751683
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD29,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochromes c,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor CHOP,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0022-2828
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
42
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
653-61
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:17292911-Aging,
pubmed-meshheading:17292911-Animals,
pubmed-meshheading:17292911-Antigens, CD29,
pubmed-meshheading:17292911-Apoptosis,
pubmed-meshheading:17292911-Cells, Cultured,
pubmed-meshheading:17292911-Cytochromes c,
pubmed-meshheading:17292911-Cytosol,
pubmed-meshheading:17292911-Enzyme Inhibitors,
pubmed-meshheading:17292911-Gene Expression Regulation,
pubmed-meshheading:17292911-Glycogen Synthase Kinase 3,
pubmed-meshheading:17292911-Heart Ventricles,
pubmed-meshheading:17292911-Male,
pubmed-meshheading:17292911-Muscle Cells,
pubmed-meshheading:17292911-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:17292911-Rats,
pubmed-meshheading:17292911-Rats, Sprague-Dawley,
pubmed-meshheading:17292911-Receptors, Adrenergic, beta,
pubmed-meshheading:17292911-Transcription Factor CHOP
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pubmed:year |
2007
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pubmed:articleTitle |
Glycogen synthase kinase-3beta plays a pro-apoptotic role in beta-adrenergic receptor-stimulated apoptosis in adult rat ventricular myocytes: Role of beta1 integrins.
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pubmed:affiliation |
Department of Physiology, James H Quillen College of Medicine, James H Quillen Veterans Affairs Medical Center, East Tennessee State University, PO Box 70576, Johnson City, TN 37614, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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