Journal article

Publication year: 2006

Pages: 352-362

Journal: Cardiovascular Research

Volume number: 71

Issue number: 2

ISSN: 0008-6363

eISSN: 1755-3245

DOI Link: https://doi.org/10.1016/j.cardiores.2006.02.004

Publisher: Oxford University Press

Abstract: 

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 (TGF beta) 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 a-adrenoceptor stimulation.

Methods: Freshly isolated myocytes were used to examine formation of ROS via H2DCF fluorescence. p38 MAPK phosphorylation, p70(S6-)kinase phosphorylation, PI 3-kinase, and TGF beta expression were measured by Western blotting. Sense and antisense oligonucleotides were used to down-regulate diverse PI 3-kinase isoforms. Hypertrophy was measured by C-14-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 TGF beta expression. Down-regulation of the p110 beta isoform by antisense oligonucleotides inhibited the angiotensin II-induced signalling pathway but not the a-adrenoceptor-mediated hypertrophic growth of cardiomyocytes. In contrast, down-regulation of the p110 alpha isoform decreased the a-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 11 and a-adrenoceptor stimulation as relates to hypertrophy. (c) 2006 European Society of Cardiology. Published by Elsevier B.V All rights reserved.

Harvard Citation style: Wenzel, S., Abdallah, Y., Helmig, S., Schaefer, C., Piper, H. and Schlueter, K. (2006) Contribution of PI 3-kinase isoforms to angiotensin II- and α-adrenoceptor-mediated signalling pathways in cardiomyocytes, Cardiovascular Research, 71(2), pp. 352-362. https://doi.org/10.1016/j.cardiores.2006.02.004

APA Citation style: Wenzel, S., Abdallah, Y., Helmig, S., Schaefer, C., Piper, H., & Schlueter, K. (2006). Contribution of PI 3-kinase isoforms to angiotensin II- and α-adrenoceptor-mediated signalling pathways in cardiomyocytes. Cardiovascular Research. 71(2), 352-362. https://doi.org/10.1016/j.cardiores.2006.02.004