Early NADPH oxidase-2 activation is crucial in phenylephrine-induced hypertrophy of H9c2 cells |
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| Institution: | 1. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands;2. Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands;3. Department of Cardiac Surgery, VU University Medical Center, Amsterdam, The Netherlands;4. Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands;5. Department of Pharmacology and Chemical Biology, Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA;6. ICaR-VU, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands;1. Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA;2. Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA;3. Department of Orthopaedic Surgery, Mie University School of Medicine, Mie 514, Japan;4. Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA;1. Department of Experimental and Clinical Medicine, University of Florence, Centre for the study at molecular and clinical level of chronic, degenerative and neoplastic diseases to develop novel therapies, University of Florence, Florence, Italy;2. Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy;3. Centro S.Maria agli Ulivi, Fondazione Don Carlo Gnocchi Onlus IRCCS, Impruneta, Florence, Italy;1. Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223, USA;2. Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA;1. Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA;2. Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA;1. Department of Pharmacology, University Medical Center Göttingen, Göttingen, Germany;2. Institute of Clinical Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;3. DZHK (German Centre for Cardiovascular Research) partner site Hamburg/Kiel/Lübeck, Hamburg, Germany;4. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA;5. Institut Curie, CNRS UMR 3347, INSERM U1021, Paris Sud University Centre de Recherche, Orsay, France;6. Institute of Pharmacy, University of Hamburg, Hamburg, Germany |
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| Abstract: | Reactive oxygen species (ROS) produced by different NADPH oxidases (NOX) play a role in cardiomyocyte hypertrophy induced by different stimuli, such as angiotensin II and pressure overload. However, the role of the specific NOX isoforms in phenylephrine (PE)-induced cardiomyocyte hypertrophy is unknown. Therefore we aimed to determine the involvement of the NOX isoforms NOX1, NOX2 and NOX4 in PE-induced cardiomyocyte hypertrophy. Hereto rat neonatal cardiomyoblasts (H9c2 cells) were incubated with 100 μM PE to induce hypertrophy after 24 and 48 h as determined via cell and nuclear size measurements using digital imaging microscopy, electron microscopy and an automated cell counter. Digital-imaging microscopy further revealed that in contrast to NOX1 and NOX4, NOX2 expression increased significantly up to 4 h after PE stimulation, coinciding and co-localizing with ROS production in the cytoplasm as well as the nucleus. Furthermore, inhibition of NOX-mediated ROS production with apocynin, diphenylene iodonium (DPI) or NOX2 docking sequence (Nox2ds)-tat peptide during these first 4 h of PE stimulation significantly inhibited PE-induced hypertrophy of H9c2 cells, both after 24 and 48 h of PE stimulation. These data show that early NOX2-mediated ROS production is crucial in PE-induced hypertrophy of H9c2 cells. |
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