Melting into thin air: The role of acute hypoxia in skeletal muscle atrophy

Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, PCB125

Poster Communications: Melting into thin air: The role of acute hypoxia in skeletal muscle atrophy

B. T. Elliott1, D. Renshaw1, S. Getting1, P. Watt2, D. Howard3, R. Mackenzie1

1. University of Westminster, London, Please Select, United Kingdom. 2. Chelsea School, University of Brighton, London, United Kingdom. 3. University College Hospital, London, United Kingdom.

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Muscle is the largest tissue in the human body and the size of muscle is significantly regulated by the protein myostatin. Chronic hypoxic exposure in vivo induces muscle atrophy in both healthy mountaineers and patients with COPD. However, both COPD patients and mountaineers are difficult models to study due to several confounding factors. Chronic hypoxia in mice and COPD patients co-presents with elevated myostatin, suggestive of a causative role. We previously showed that 2 hours hypoxia induced a decrease in muscle myostatin and a trend towards increased plasma myostatin expression in healthy individuals. We therefore wished to determine the effect of time in hypoxia, hypothesizing that an increase in hypoxic exposure time would result in a greater myostatin decrease at the muscle level.Healthy males [expressed as x (± S.D), N = 8, 30 (± 4.8) years of age] were exposed to 10 hours hypoxia with muscle biopsies from vastus laterals drawn pre- and post-exposure. Plasma samples were taken pre-, 2 hours into exposure, and post-exposure. Myostatin and downstream markers of activity were quantified by western blot in muscle. Plasma myostatin was measured by ELISA. Effect of hypoxia was monitored by measurement of SpO2 & Lake Louise Acute Mountain Sickness questionnaire (LLAMS).Repeated measures ANOVA reveals participants SpO2 dropped significantly during hypoxia [97.8 % (0.4 %) vs. 77.8 % (0.69 %), p < 0.05, d > 1). Muscle myostatin peptide showed strong trends towards increasing, with a 44 % increase from control (P = 0.06, d = 0.62). The precursor propeptide of myostatin did not increase. Downstream of myostatin, pAkt (t473) and total Akt did not increase. Here we have shown that muscle myostatin appears to increase following 10 hours of hypoxia in healthy humans. Counter to our 2 hours results where muscle myostatin decreased, these results show a trend towards an increase in muscle myostatin, suggesting a time-dependent change in myostatin expression following hypoxic exposure. These results may explain in part the muscle atrophy seen in chronic hypoxic conditions such as COPD and mountaineering. Future work will examine the effect of dose of hypoxia upon myostatin expression in healthy individuals.



Where applicable, experiments conform with Society ethical requirements.

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