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β1-Integrin is up-regulated via Rac1-dependent reactive oxygen species as part of the hypertrophic cardiomyocyte response

Hauselmann, S. P. and Rosc-Schluter, B. I. and Lorenz, V. and Plaisance, I. and Brink, M. and Pfister, O. and Kuster, G. M.. (2011) β1-Integrin is up-regulated via Rac1-dependent reactive oxygen species as part of the hypertrophic cardiomyocyte response. Free radical biology & medicine, Vol. 51, H. 3. pp. 609-618.

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Official URL: http://edoc.unibas.ch/dok/A6338355

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Abstract

beta(1)-Integrin mediates cardiomyocyte growth and survival and its proper regulation is essential for the structural and functional integrity of the heart. beta(1)-Integrin expression is enhanced in hypertrophy, but the mechanism and significance of its up-regulation are unknown. Because reactive oxygen species (ROS) are important mediators of myocardial remodeling we examined their role in regulated beta(1)-integrin expression. Hypertrophy was induced in neonatal cardiomyocytes by endothelin-1 (ET-1), which activated the regulatory NADPH oxidase subunit Rac1, evoked ROS, and enhanced fetal gene expression and cardiomyocyte size. ET-1 also enhanced cell adhesion and FAK phosphorylation and inhibited oxidative stress-induced cardiomyocyte apoptosis. Further, ET-1 increased beta(1)-integrin mRNA and protein expression via Rac1-ROS-dependent MEK/ERK and EGF receptor-PI3K/Akt activation as shown by adenoviral dominant-negative Rac1 or overexpression of copper/zinc-superoxide dismutase. The relevance of regulated beta(1)-integrin expression was examined in cardiomyocytes, in which targeting siRNA impeded the ET-1-induced beta(1)-integrin up-regulation. In these cells, ET-1-induced cell adhesion, FAK phosphorylation, and hypertrophic response were significantly blunted, whereas its antiapoptotic effect was predominantly unchanged, suggesting at least partial dissociation of prohypertrophic and prosurvival signaling elicited by ET-1. In conclusion, beta(1)-integrin up-regulation in response to ET-1 is mediated via Rac1-ROS-dependent activation of prohypertrophic pathways and is mandatory for ET-1-induced FAK activation, cell adhesion, and hypertrophic response.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Myocardial Research (Kuster Pfister)
03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Kardiologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Kardiologie
03 Faculty of Medicine > Departement Biomedizin > Division of Physiology > CardioBiology (Brink)
UniBasel Contributors:Pfister, Otmar and Brink, Marijke and Kuster Pfister, Gabriela
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Pergamon Press
ISSN:0891-5849
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 May 2015 08:44
Deposited On:10 Apr 2015 09:13

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