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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Ciencias Cardiovasculares > Cardiopatía hipertensiva > DA - CIMA - Cardiovasculares - Cardiopatía hipertensiva - Artículos de Revista >

Overexpression of human truncated peroxisome proliferator-activated receptor alpha induces apoptosis in HL-1 cardiomyocytes
Authors: Beaumont, J. (Javier)
Arias, T. (Teresa)
Ravassa, S. (Susana)
Diez, J. (Javier)
Keywords: Truncated PPARα
Apoptosis
Cardiomyocytes
Issue Date: 2008
Publisher: Oxford University Press
Publisher version: http://cardiovascres.oxfordjournals.org/content/79/3/458
ISSN: 1755-3245
Citation: Beaumont J, Arias T, Ravassa S, Diez J. Overexpression of human truncated peroxisome proliferator-activated receptor alpha induces apoptosis in HL-1 cardiomyocytes. Cardiovasc Res 2008 Aug 1;79(3):458-463.
Abstract
AIMS: Our goal was to analyse whether truncated peroxisome proliferator-activated receptor alpha (PPARalpha) overexpression induces apoptosis of cardiomyocytes. METHODS AND RESULTS: We constructed a recombinant vector of human truncated PPARalpha and a mammalian expression vector to transfect PPARalpha into a line of murine cardiomyocytes designated HL-1. Four hallmarks of apoptosis were measured in these transfected cells: depolarization of mitochondrial membrane, activation of caspase-3, phosphatidylserine (PS) externalization, and DNA fragmentation. Co-transfection with human cyclic adenosine monophosphate response element-binding protein (CREB) and human CREB binding protein (CBP) and analysis of apoptosis regulatory proteins, Bcl-2 and Bax, were also performed in truncated PPARalpha-transfected cells to determine the potential mechanisms by which truncated PPARalpha may influence apoptosis. Progressive depolarization of mitochondrial membrane, activation of caspase-3, PS externalization, DNA fragmentation, and cell death were observed in HL-1 cells upon increasing levels of transfected truncated PPARalpha. The expression of the antiapoptotic protein Bcl-2 decreased in transfected HL-1 cardiomyocytes, whereas no changes in the proapoptotic protein Bax were observed in these cells. Overexpression of CREB plus CBP abolished the inhibitory effect of truncated PPARalpha on Bcl-2 protein. CONCLUSION: These results demonstrate that human truncated PPARalpha overexpression induces apoptosis in HL-1 cardiomyocytes. In addition, our findings suggest that truncated PPARalpha may induce cardiomyocyte apoptosis through the inhibition of the antiapoptotic protein, Bcl-2. It is proposed that competition with CREB for coactivators like CBP could be involved in this inhibitory effect.
Permanent link: http://hdl.handle.net/10171/21850
Appears in Collections:DA - CIMA - Cardiovasculares - Cardiopatía hipertensiva - Artículos de Revista

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