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

Nynke E Hahn1, René J P Musters2, Jan M Fritz3

  • 1Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; ICaR-VU, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.

Cellular Signalling
|May 6, 2014
PubMed

Insights

Early production of reactive oxygen species (ROS) by NADPH oxidase 2 (NOX2) is crucial for phenylephrine-induced cardiomyocyte hypertrophy. Inhibiting NOX2-mediated ROS significantly reduced hypertrophy in H9c2 cells.

Area of Science:

  • Cardiovascular Biology
  • Cell Signaling
  • Oxidative Stress

Background:

  • Reactive oxygen species (ROS) produced by NADPH oxidases (NOX) are implicated in cardiomyocyte hypertrophy.
  • The specific roles of NOX isoforms in phenylephrine (PE)-induced hypertrophy remain unclear.

Purpose of the Study:

  • To investigate the involvement of NOX isoforms (NOX1, NOX2, NOX4) in PE-induced cardiomyocyte hypertrophy.
  • To determine the role of early NOX-mediated ROS production in this process.

Main Methods:

  • Rat neonatal cardiomyoblasts (H9c2 cells) were stimulated with PE to induce hypertrophy.
  • Cell and nuclear sizes were measured using digital imaging and electron microscopy.
  • NOX isoform expression, ROS production, and the effects of NOX inhibitors (apocynin, DPI, Nox2ds-tat) were assessed.

Main Results:

  • PE stimulation increased NOX2 expression and ROS production within 4 hours, co-localizing in cytoplasm and nucleus.
  • NOX1 and NOX4 expression did not significantly increase.
  • Inhibition of NOX-mediated ROS during the initial 4 hours of PE exposure significantly reduced H9c2 cell hypertrophy at 24 and 48 hours.

Conclusions:

  • Early NOX2-mediated ROS production is a critical early event in PE-induced cardiomyocyte hypertrophy.
  • Targeting NOX2-derived ROS may offer a therapeutic strategy for preventing or treating cardiac hypertrophy.
Keywords:
Cardiomyocyte hypertrophyNADPH oxidaseNOX2Phenylephrine

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