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J Physiol Volume 586, Number 16, 3979-3990, August 15, 2008 DOI: 10.1113/jphysiol.2008.155382
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SKELETAL MUSCLE AND EXERCISE

Repeated bouts of aerobic exercise lead to reductions in skeletal muscle free radical generation and nuclear factor {kappa}B activation

 Susan V. Brooks1, Aphrodite Vasilaki2, Lisa M. Larkin1, Anne McArdle2 and Malcolm J. Jackson2

1 Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA
2 Division of Metabolic and Cellular Medicine, School of Clinical Sciences, University of Liverpool, Liverpool, UK

Chronic exercise improves endurance and skeletal muscle oxidative capacity. Despite the potential importance of reactive oxygen species (ROS) generated during exercise as regulators of these adaptations, the effect of repeated bouts of aerobic exercise on ROS generation by skeletal muscles during contractions has not been examined. Our aim was to establish the impact of repeated treadmill running exercise on muscle ROS generation and activation of redox-sensitive transcription factors. Following 8 weeks of treadmill running, mice displayed an improvement in running speed that was associated with an enhanced ability of gastrocnemius (GTN) muscles to maintain force during a protocol of isometric contractions. In contrast to GTN muscles of cage-sedentary (Sed) mice, muscles from exercised (Exer) mice did not release superoxide or nitric oxide during the isometric contractions. For male mice, basal levels of nuclear factor {kappa}B (NF{kappa}B) and activator protein-1 (AP-1) DNA binding were increased by treadmill running, and the contraction-induced activation of NF{kappa}B and AP-1 observed in muscles of Sed mice was absent in Exer muscles. Also in contrast to Sed muscles, Exer muscles displayed no reductions in glutathione or protein thiol levels in response to contraction. Our observations of decreases for Exer compared with Sed muscles in contraction-induced (i) ROS generation, (ii) activation of redox-sensitive signalling pathways, and (iii) ROS stress suggest that exercise conditioning enhances the ability of skeletal muscle to readily and rapidly detoxify ROS and/or reduces ROS generation, providing protection from ROS-induced damage and reducing signals that might act to mediate further unnecessary adaptations.

(Received 17 April 2008; accepted after revision 16 June 2008; first published online 26 June 2008)
Corresponding author S.V. Brooks: 2029 Biomedical Science Research Building, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.  Email: svbrooks{at}umich.edu






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