Decreasing xanthine oxidase-mediated oxidative stress prevents useful cellular adaptations to exercise in rats.
Reactive oxygen or nitrogen species (RONS) are produced during exercise due, at least in part, to the activation of xanthine oxidase. When exercise is exhaustive they cause tissue damage; however, they may also act as signals inducing specific cellular adaptations to exercise. We have tested this hypothesis by studying the effects of allopurinol-induced inhibition of RONS production on cell signalling pathways in rats submitted to exhaustive exercise. Exercise caused an activation of mitogen-activated protein kinases (MAPKs: p38, ERK 1 and ERK 2), which in turn activated nuclear factor kappaB (NF-kappaB) in rat gastrocnemius muscle. This up-regulated the expression of important enzymes associated with cell defence (superoxide dismutase) and adaptation to exercise (eNOS and iNOS). All these changes were abolished when RONS production was prevented by allopurinol. Thus we report, for the first time, evidence that decreasing RONS formation prevents activation of important signalling pathways, predominantly the MAPK-NF-kappaB pathway; consequently the practice of taking antioxidants before exercise may have to be re-evaluated.
Gomez-Cabrera
Mari-Carmen
MC
Catholic University of Valencia, Spain.
Borrás
Consuelo
C
Pallardó
Federico V
FV
Sastre
Juan
J
Ji
Li Li
LL
Viña
Jose
J
D000222:Adaptation, Physiological / Q000502:physiology*; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress / Q000502:physiology*; D005082:Physical Exertion / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*
D004791:Enzyme Inhibitors; D016328:NF-kappa B; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D000493:Allopurinol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D048049:Extracellular Signal-Regulated MAP Kinases