Early NADPH oxidase-2 activation is crucial in phenylephrine-induced hypertrophy of H9c2 cells

N.E. Hahn, R.J.P. Musters, J.M. Fritz, P.J. Pagano, A.B.A. Vonk, W.J. Paulus, A.C. van Rossum, C. Meischl, H.W.M. Niessen, P.A.J. Krijnen

Research output: Contribution to journalArticleAcademicpeer-review

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 48h 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 4h 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 4h of PE stimulation significantly inhibited PE-induced hypertrophy of H9c2 cells, both after 24 and 48h of PE stimulation. These data show that early NOX2-mediated ROS production is crucial in PE-induced hypertrophy of H9c2 cells.

Original languageEnglish
Pages (from-to)1818-1824
Number of pages7
JournalCellular Signalling
Volume26
Issue number9
DOIs
Publication statusPublished - Sep 2014

Cite this

@article{100675ea030d412b85cf755e0ca29327,
title = "Early NADPH oxidase-2 activation is crucial in phenylephrine-induced hypertrophy of H9c2 cells",
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 48h 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 4h 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 4h of PE stimulation significantly inhibited PE-induced hypertrophy of H9c2 cells, both after 24 and 48h of PE stimulation. These data show that early NOX2-mediated ROS production is crucial in PE-induced hypertrophy of H9c2 cells.",
keywords = "Acetophenones, Animals, Cell Line, Enzyme Activation, Hypertrophy, Membrane Glycoproteins, NADH, NADPH Oxidoreductases, NADPH Oxidase 1, NADPH Oxidase 2, NADPH Oxidase 4, NADPH Oxidases, Onium Compounds, Phenylephrine, Rats, Reactive Oxygen Species, Journal Article, Research Support, Non-U.S. Gov't",
author = "N.E. Hahn and R.J.P. Musters and J.M. Fritz and P.J. Pagano and A.B.A. Vonk and W.J. Paulus and {van Rossum}, A.C. and C. Meischl and H.W.M. Niessen and P.A.J. Krijnen",
note = "Copyright {\circledC} 2014 Elsevier Inc. All rights reserved.",
year = "2014",
month = "9",
doi = "10.1016/j.cellsig.2014.04.018",
language = "English",
volume = "26",
pages = "1818--1824",
journal = "Cellular Signalling",
issn = "0898-6568",
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Early NADPH oxidase-2 activation is crucial in phenylephrine-induced hypertrophy of H9c2 cells. / Hahn, N.E.; Musters, R.J.P.; Fritz, J.M.; Pagano, P.J.; Vonk, A.B.A.; Paulus, W.J.; van Rossum, A.C.; Meischl, C.; Niessen, H.W.M.; Krijnen, P.A.J.

In: Cellular Signalling, Vol. 26, No. 9, 09.2014, p. 1818-1824.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Early NADPH oxidase-2 activation is crucial in phenylephrine-induced hypertrophy of H9c2 cells

AU - Hahn, N.E.

AU - Musters, R.J.P.

AU - Fritz, J.M.

AU - Pagano, P.J.

AU - Vonk, A.B.A.

AU - Paulus, W.J.

AU - van Rossum, A.C.

AU - Meischl, C.

AU - Niessen, H.W.M.

AU - Krijnen, P.A.J.

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2014/9

Y1 - 2014/9

N2 - 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 48h 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 4h 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 4h of PE stimulation significantly inhibited PE-induced hypertrophy of H9c2 cells, both after 24 and 48h of PE stimulation. These data show that early NOX2-mediated ROS production is crucial in PE-induced hypertrophy of H9c2 cells.

AB - 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 48h 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 4h 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 4h of PE stimulation significantly inhibited PE-induced hypertrophy of H9c2 cells, both after 24 and 48h of PE stimulation. These data show that early NOX2-mediated ROS production is crucial in PE-induced hypertrophy of H9c2 cells.

KW - Acetophenones

KW - Animals

KW - Cell Line

KW - Enzyme Activation

KW - Hypertrophy

KW - Membrane Glycoproteins

KW - NADH, NADPH Oxidoreductases

KW - NADPH Oxidase 1

KW - NADPH Oxidase 2

KW - NADPH Oxidase 4

KW - NADPH Oxidases

KW - Onium Compounds

KW - Phenylephrine

KW - Rats

KW - Reactive Oxygen Species

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.cellsig.2014.04.018

DO - 10.1016/j.cellsig.2014.04.018

M3 - Article

VL - 26

SP - 1818

EP - 1824

JO - Cellular Signalling

JF - Cellular Signalling

SN - 0898-6568

IS - 9

ER -