Skeletal muscle signaling, metabolism, and performance during sprint exercise in severe acute hypoxia after the ingestion of antioxidants

J Appl Physiol (1985). 2017 Nov 1;123(5):1235-1245. doi: 10.1152/japplphysiol.00384.2017. Epub 2017 Aug 17.


The aim of this study was to determine if reactive oxygen species (ROS) could play a role in blunting Thr172-AMP-activated protein kinase (AMPK)-α phosphorylation in human skeletal muscle after sprint exercise in hypoxia and to elucidate the potential signaling mechanisms responsible for this response. Nine volunteers performed a single 30-s sprint (Wingate test) in two occasions while breathing hypoxic gas ([Formula: see text] = 75 mmHg): one after the ingestion of placebo and another following the intake of antioxidants (α-lipoic acid, vitamin C, and vitamin E), with a randomized double-blind design. Vastus lateralis muscle biopsies were obtained before, immediately after, and 30- and 120-min postsprint. Compared with the control condition, the ingestion of antioxidants resulted in lower plasma carbonylated proteins, attenuated elevation of the AMP-to-ATP molar ratio, and reduced glycolytic rate (P < 0.05) without significant effects on performance or V̇o2 The ingestion of antioxidants did not alter the basal muscle signaling. Thr172-AMPKα and Thr184/187-transforming growth factor-β-activated kinase 1 (TAK1) phosphorylation were not increased after the sprint regardless of the ingestion of antioxidants. Thr286-CaMKII phosphorylation was increased after the sprint, but this response was blunted by the antioxidants. Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation increased immediately after the sprints coincident with increased Akt phosphorylation. In summary, antioxidants attenuate the glycolytic response to sprint exercise in severe acute hypoxia and modify the muscle signaling response to exercise. Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation, a known mechanism of Thr172-AMPKα phosphorylation inhibition, is increased immediately after sprint exercise in hypoxia, probably by a mechanism independent of ROS.NEW & NOTEWORTHY The glycolytic rate is increased during sprint exercise in severe acute hypoxia. This study showed that the ingestion of antioxidants before sprint exercise in severe acute hypoxia reduced the glycolytic rate and attenuated the increases of the AMP-to-ATP and the reduction of the NAD+-to-NADH.H+ ratios. This resulted in a modified muscle signaling response with a blunted Thr286-CaMKII but similar AMP-activated protein kinase phosphorylation responses in the sprints preceded by the ingestion of antioxidants.

Keywords: adenosine 5′-monophosphate-activated protein kinase; human; hypoxia; oxidative stress; skeletal muscle; sprint exercise.

MeSH terms

  • Acute Disease
  • Adult
  • Antioxidants / administration & dosage*
  • Athletic Performance / physiology*
  • Biomarkers / blood
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Exercise / physiology*
  • Exercise Test / methods
  • Humans
  • Hypoxia / drug therapy
  • Hypoxia / metabolism*
  • Male
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Running / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Young Adult


  • Antioxidants
  • Biomarkers
  • Blood Glucose
  • Reactive Oxygen Species