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Acute hypoxia rapidly alters myotube size in vitro and myostatin signalling in vivo (1167.1)
Author(s) -
Elliott Bradley,
Renshaw Derek,
Getting Stephen,
Watt Peter,
MacKenzie Richard
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1167.1
Subject(s) - myostatin , myogenesis , medicine , endocrinology , hypoxia (environmental) , muscle atrophy , atrophy , skeletal muscle , myocyte , biology , western blot , in vivo , chemistry , biochemistry , organic chemistry , oxygen , gene , microbiology and biotechnology
Skeletal muscle loss correlates with mortality across chronic pathological disorders. Chronic O 2 reduction induces atrophy in healthy mountaineers and hypoxemic COPD patients. Hypoxic rats and hypoxemic COPD patients show elevated myostatin expression, a regulator of muscle protein turnover and satellite cell proliferation. We hypothesized hypoxia induces atrophy via myostatin signalling. C2C12 myoblasts (N = 3) were scratched and exposed to 18 hrs of 21% or 1% O 2 +/‐ 10 µM PS145 (NF‐κB inhibitor) to measure migration. Myotubes (N = 3) were exposed to 2, 24 or 48 hr of 21% or 1% O 2 +/‐ 10 µM PS145 to measure atrophy. Healthy males (N = 9) were exposed to 12% O 2 for 2 hours with muscle tissue and plasma collected pre‐ and post‐exposure. Protein expression was quantified by Western blot (muscle) or ELISA (plasma). Hypoxic myoblasts showed reduced migration. Hypoxic myotubes showed atrophy at 2 hr, which increased at 24 and 48 hr. Hypoxic impairment of myoblast migration and myotube atrophy was offset by PS1145 incubation. Hypoxic participants showed reduced muscle myostatin, and trends for increased ubiquitin binding and NF‐κB activity. Plasma myostatin was unchanged. Here we demonstrate hypoxia rapidly induces atrophy in vitro via NF‐κB dependent mechanisms. Hypoxia alone induces atrophy, independent of other factors, and an atrophic environment in vivo similar to that seen in chronic hypoxic disorders, such as COPD. Grant Funding Source : Supported by The Society for Endocrinology (UK)