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Involvement of FrzA/sFRP-1 and the Wnt/frizzled pathway in ischemic preconditioning.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Barandon, Laurent Dufourcq, Pascale Costet, Pierre Moreau, Catherine Allières, Cécile Daret, Daniéle Santos, Pierre Dos Lamazière, Jean-Marie Daniel Couffinhal, Thierry Duplaa, Cecile |
| Copyright Year | 2005 |
| Abstract | 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. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://circres.ahajournals.org/content/circresaha/96/12/1299.full.pdf |
| Alternate Webpage(s) | http://circres.ahajournals.org/content/circresaha/96/12/1299.full.pdf?download=true |
| PubMed reference number | 15920021v1 |
| Volume Number | 96 |
| Issue Number | 12 |
| Journal | Circulation research |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Catenins Cell secretion Doxycycline Glycogen (Starch) Synthase Glycogen Synthase Kinases Infarction Large Mice, Transgenic Myocytes, Cardiac Nitric Oxide Synthase Preconditioning Protein Kinase C Protein Kinases Proto-Oncogene Proteins c-akt SFRP1 wt Allele Transient Ischemic Attack beta catenin eIF-2 Kinase frizzled related protein-1 glycogen synthase kinase 3 beta tetrandrine |
| Content Type | Text |
| Resource Type | Article |
