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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2005-6-24
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pubmed:abstractText |
Phosphorylation and subsequent inactivation of glycogen synthase kinase (GSK)-3beta via the Akt/PI3-Kinase pathway during ischemic preconditioning (PC) has been shown to be cardioprotective. As FrzA/sFRP-1, a secreted antagonist of the Wnt/Frizzled pathway, is expressed in the heart and is able to decrease the phosphorylation of GSK-3beta in vitro on vascular cells, we examined its effect during PC using transgenic mouse overexpressing FrzA in cardiomyocytes (alpha-MHC promoter) under a conditional transgene expression approach (tet-off system). Overexpression of FrzA inhibited the increase in GSK-3beta phosphorylation as well as protein kinase C (PKC) epsilon activation in transgenic mice after PC as compared with littermates. Phospho-Akt (P-Akt), phospho-JNK, or the cytoplasmic beta-catenin levels were not modified, phospho-p38 (P-p38) was slightly increased in transgenic mice after PC as compared with littermates. FrzA transgenic mice displayed a larger infarct size and a greater worsening of cardiac function compared with littermates. All these differences were reversed by the addition of doxycycline. This study demonstrates for the first time that disruption of a beta-catenin independent Wnt/Frizzled pathway induces the activation of GSK-3beta and reverses the benefit of preconditioning.
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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/Catnb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Doxycycline,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
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/Sfrp1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1524-4571
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
24
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pubmed:volume |
96
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1299-306
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:15920021-Animals,
pubmed-meshheading:15920021-Cytoskeletal Proteins,
pubmed-meshheading:15920021-Doxycycline,
pubmed-meshheading:15920021-Glycogen Synthase Kinase 3,
pubmed-meshheading:15920021-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:15920021-Ischemic Preconditioning, Myocardial,
pubmed-meshheading:15920021-Membrane Proteins,
pubmed-meshheading:15920021-Mice,
pubmed-meshheading:15920021-Mice, Transgenic,
pubmed-meshheading:15920021-Myocardial Infarction,
pubmed-meshheading:15920021-Phosphorylation,
pubmed-meshheading:15920021-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15920021-Proto-Oncogene Proteins,
pubmed-meshheading:15920021-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15920021-Signal Transduction,
pubmed-meshheading:15920021-Trans-Activators,
pubmed-meshheading:15920021-Wnt Proteins,
pubmed-meshheading:15920021-beta Catenin,
pubmed-meshheading:15920021-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2005
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pubmed:articleTitle |
Involvement of FrzA/sFRP-1 and the Wnt/frizzled pathway in ischemic preconditioning.
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pubmed:affiliation |
Department of Cardiovascular Surgery, Hôpital Haut Lévêque, Pessac, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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