Myostatin up-regulation is associated with the skeletal muscle response to hypoxic stimuli.
Myostatin and hypoxia signalling pathways are able to induce skeletal muscle atrophy, but whether a relationship between these two pathways exists is currently unknown. Here, we tested the hypothesis that a potential mechanism for hypoxia effect on skeletal muscle may be through regulation of myostatin. We reported an induction of myostatin expression in muscles of rats exposed to chronic hypoxia. Interestingly, we also demonstrated increased skeletal muscle myostatin protein expression in skeletal muscle of hypoxemic patients with severe chronic obstructive pulmonary disease (COPD). Parallel studies in human skeletal muscle cell cultures showed that induction of myostatin expression in myotubes treated with hypoxia-mimicking agent such as cobalt chloride (CoCl(2)) is associated with myotube atrophy. Furthermore, we demonstrated that inhibition of myostatin by means of genetic deletion of myostatin or treatment with blocking antimyostatin antibodies inhibits the CoCl(2)-induced atrophy in muscle cells. Finally, addition of recombinant myostatin restored the CoCl(2)-induced atrophy in myostatin deficient myotubes. These results strongly suggest that myostatin can play an essential role in the adaptation of skeletal muscle to hypoxic environment.
Hayot
Maurice
M
INSERM, ERI 25-Muscle et Pathologies, Hôpital Arnaud de Villeneuve, Bât. A Craste de Paulet, F-34295 Montpellier, France.
Rodriguez
Julie
J
Vernus
Barbara
B
Carnac
Gilles
G
Jean
Elise
E
Allen
David
D
Goret
Lucie
L
Obert
Philippe
P
Candau
Robin
R
Bonnieu
Anne
A
D000328:Adult; D000368:Aged; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology; D001835:Body Weight; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000139:chemically induced; D055435:Myostatin / Q000235:genetics / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation
D016587:Antimutagenic Agents; D009124:Muscle Proteins; D055435:Myostatin; D011994:Recombinant Proteins; D003035:Cobalt; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; C018021:cobaltous chloride