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|
|Issue Date: ||2008|
|Publisher: ||Oxford University Press|
|Publisher version: ||http://cardiovascres.oxfordjournals.org/content/79/3/458|
|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.|
|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|
|Files in This Item:|
There are no files associated with this item.
Items in Dadun are protected by copyright, with all rights reserved, unless otherwise indicated.