Inhibition of xanthine oxidase mediated reactive oxygen species during exercise attenuates mitochondrial biogenesis signalling in skeletal muscle

INTRODUCTION:We tested the hypothesis that blocking the xanthine oxidase (XO)‐mediated increase in reactive oxygen species (ROS) with allopurinol during treadmill running in rats would inhibit phosphorylation of several key mitochondrial biogenesis signalling proteins.METHODS:Sprague Dawley rats rested (rest), exercised (Ex) or exercised following 30min pretreatment with 32 mg/kg of allopurinol by IP injection (Ex+allo). The exercise groups ran on a treadmill for 60 min (25m/min, 5% incline). Mitochondrial biogenesis signalling proteins were examined in the whole cell (phosphorylated p38 MAPK and AMPK) and nuclear fraction (phosphorylated CREB and ATF‐2) of the gastrocnemius via immunoblotting.RESULTS:Allopurinol treatment abolished the exercise‐induced phosphorylation of p38MAPK and ATF‐2 (P<0.05). There was a tendency (P=0.07) for exercise to increase phosphorylation of AMPK and allopurinol had no effect on this. CREB phosphorylation was not significantly different between groups.CONCLUSION:This data suggests that XO‐mediated increases in ROS during exercise are involved in some aspects of mitochondrial biogenesis signalling following exercise in skeletal muscle. Further studies are needed to examine if other aspects of the mitochondrial biogenesis pathway (eg PGC‐1 and NRF‐1) are also are also inhibited by allopurinol treatment during exercise.