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Decreasing xanthine oxidase-mediated oxidative stress prevents useful cellular adaptations to exercise in rats
Mari-Carmen Gomez-Cabrera1, Consuelo Borrás, Federico V Pallardó
1Catholic University of Valencia, Spain.
Abstract:
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.
Insights
Exhaustive exercise produces reactive oxygen species (RONS) that signal cellular adaptations. Inhibiting RONS production with allopurinol blocked these exercise-induced signalling pathways, suggesting antioxidants may need re-evaluation.
Area of Science:
- Exercise physiology
- Cellular signaling
- Biochemistry
Background:
- Reactive oxygen and nitrogen species (RONS) are byproducts of exercise, potentially mediating cellular adaptations.
- Xanthine oxidase activation contributes to RONS production during physical activity.
- While high levels of RONS cause damage, lower levels may act as signaling molecules.
Purpose of the Study:
- To investigate the role of RONS in exercise-induced cellular adaptations.
- To examine the impact of inhibiting RONS production on cell signaling pathways during exhaustive exercise.
- To determine if RONS mediate the activation of specific signaling cascades in response to exercise.
Main Methods:
- Utilized a rat model subjected to exhaustive exercise.
- Administered allopurinol to inhibit RONS production.
- Analyzed the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappaB (NF-kappaB) signaling.
- Measured the expression of antioxidant and adaptive enzymes (superoxide dismutase, eNOS, iNOS).
Main Results:
- Exhaustive exercise activated MAPK (p38, ERK1/2) and NF-kappaB signaling pathways in rat gastrocnemius muscle.
- This activation led to increased expression of superoxide dismutase, eNOS, and iNOS.
- Allopurinol treatment abolished these exercise-induced signaling events and enzyme expression changes.
- RONS production is critical for mediating exercise-induced activation of the MAPK-NF-kappaB pathway.
Conclusions:
- RONS, particularly via the MAPK-NF-kappaB pathway, are essential mediators of cellular adaptations to exhaustive exercise.
- Inhibition of RONS production prevents exercise-induced signaling and adaptive responses.
- The use of antioxidants prior to exercise may interfere with beneficial exercise adaptations and warrants re-evaluation.
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