Copyright © 2006, European Society of Cardiology
Contribution of PI 3-kinase isoforms to angiotensin II- and 
-adrenoceptor-mediated signalling pathways in cardiomyocytes
Physiologisches Institut, Justus-Liebig-Universität, Aulweg 129, D-35392 Giessen, Germany
* Corresponding author. Tel.: +49 641 99 47 255; fax: +49 641 99 47 219. Email address: sibylle.wenzel{at}physiologie.med.uni-giessen.de
Objective Angiotensin II stimulation increases the formation of reactive oxygen species (ROS), the phosphorylation of p38 mitogen-activated protein kinase (MAPK), and the expression of transforming growth factor beta (TGFβ) in adult cardiomyocytes. The aim of this study was to determine the involvement of PI 3-kinase and to specify the participation of different isoforms in the angiotensin II-induced formation of ROS in comparison to the hypertrophic pathway triggered by 
-adrenoceptor stimulation.
Methods Freshly isolated myocytes were used to examine formation of ROS via H2DCF fluorescence. p38 MAPK phosphorylation, p70S6-kinase phosphorylation, PI 3-kinase, and TGFβ expression were measured by Western blotting. Sense and antisense oligonucleotides were used to down-regulate diverse PI 3-kinase isoforms. Hypertrophy was measured by 14C-phenylalanine incorporation and cell volume.
Results Inhibition of PI 3-kinase by Ly294002 or wortmannin, two inhibitors, decreased formation of ROS, phosphorylation of p38 MAPK, and TGFβ expression. Down-regulation of the p110β isoform by antisense oligonucleotides inhibited the angiotensin II-induced signalling pathway but not the -adrenoceptor-mediated hypertrophic growth of cardiomyocytes. In contrast, down-regulation of the p110 isoform decreased the -adrenoceptor-mediated hypertrophic growth of cardiomyocytes but did not affect the angiotensin II-mediated signalling pathway.
Conclusion Thus, our study identifies an involvement of PI 3-kinase in the angiotensin II-induced formation of ROS and provides a biochemical basis for ligand-specific responses for angiotensin II and -adrenoceptor stimulation as relates to hypertrophy.
KEYWORDS Reactive oxygen species; p38 MAPK; TGFβ; Antisense oligonucleotides; Hypertrophy
Time for primary review 30 days
Ajay Shah, King's College, London, served as Guest Editor for this article.
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