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NOX2 Inhibition Impairs Early Muscle Gene Expression Induced by a Single Exercise Bout

Carlos Henríquez-Olguín1, Alexis Díaz-Vegas2, Yildy Utreras-Mendoza2

  • 1Facultad de Medicina, Centro de Estudios Moleculares de la Célula, Instituto de Ciencias Biomédicas, Universidad de ChileSantiago, Chile; Laboratory of Exercise Sciences, Clínica MEDSSantiago, Chile.

Frontiers in Physiology
|July 30, 2016
PubMed

Insights

Skeletal muscle NADPH oxidase isoform 2 (NOX2) is crucial for signaling during exercise. Inhibiting NOX2 with apocynin alters molecular responses and reduces exercise-induced IL-6, highlighting NOX2

Area of Science:

  • Exercise physiology
  • Skeletal muscle biology
  • Molecular signaling

Background:

  • Reactive oxygen species (ROS) are signaling molecules in skeletal muscle during exercise.
  • The precise sources and molecular mechanisms of exercise-induced ROS remain unclear.
  • NADPH oxidase isoform 2 (NOX2) is a potential source of ROS in skeletal muscle.

Purpose of the Study:

  • To investigate the role of skeletal muscle NOX2 in the molecular response to physical exercise.
  • To determine if NOX2 inhibition affects exercise-induced signaling pathways and gene expression.

Main Methods:

  • BALB/c mice were pre-treated with a NOX2 inhibitor (apocynin) or vehicle before swim exercise.
  • NOX2 activation, complex assembly, and downstream signaling pathways (p38 MAPK, ERK1/2, NF-κB) were assessed.
  • mRNA levels of antioxidant enzymes and mitochondrial markers were quantified.
  • In vitro models using gp91-dstat were also employed.

Main Results:

  • Exercise upregulated phospho-p47(phox) and NOX2 complex assembly in skeletal muscle.
  • Apocynin treatment inhibited exercise-induced NOX2 activation and downstream signaling.
  • Exercise increased MnSOD, GPx, CS, tfam, and IL-6 mRNA, which was blunted by apocynin.
  • Apocynin reduced exercise-induced plasma IL-6 levels.

Conclusions:

  • Skeletal muscle NOX2 plays a critical role in the molecular response to acute exercise.
  • NOX2 inhibition alters intracellular signaling and gene expression in response to exercise stimuli.
  • Targeting NOX2 may modulate the adaptive response to physical activity.
Keywords:
IL-6NADPH oxidaseantioxidant defensemuscle adaptationreactive oxygen speciesredox signaling

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