nNOS regulation of skeletal muscle fatigue and exercise performance

Biophysics Reviews
Justin M Percival

Abstract

Neuronal nitric oxide synthases (nNOS) are Ca(2+)/calmodulin-activated enzymes that synthesize the gaseous messenger nitric oxide (NO). nNOSμ and the recently described nNOSβ, both spliced nNOS isoforms, are important enzymatic sources of NO in skeletal muscle, a tissue long considered to be a paradigmatic system for studying NO-dependent redox signaling. nNOS is indispensable for skeletal muscle integrity and contractile performance, and deregulation of nNOSμ signaling is a common pathogenic feature of many neuromuscular diseases. Recent evidence suggests that both nNOSμ and nNOSβ regulate skeletal muscle size, strength, and fatigue resistance, making them important players in exercise performance. nNOSμ acts as an activity sensor and appears to assist skeletal muscle adaptation to new functional demands, particularly those of endurance exercise. Prolonged inactivity leads to nNOS-mediated muscle atrophy through a FoxO-dependent pathway. nNOS also plays a role in modulating exercise performance in neuromuscular disease. In the mdx mouse model of Duchenne muscular dystrophy, defective nNOS signaling is thought to restrict contractile capacity of working muscle in two ways: loss of sarcolemmal nNOSμ causes excessive ischemic dam...Continue Reading

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Citations

Sep 25, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xingcai CaiGang Shu
Oct 2, 2020·International Journal of Molecular Sciences·Jinhong MengJennifer E Morgan
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Jan 7, 2021·Cells·Luisa GorzaMara Brancaccio
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May 1, 2021·Antioxidants·Filip Kolodziej, Ken D O'Halloran
Oct 21, 2021·Exercise and Sport Sciences Reviews·Barbora PiknovaAndrew M Jones

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