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Hypoxia is able to induce proteolysis in differentiated L6 muscle cells
Author(s) -
Caron MarcAndré,
Doucet Mariève,
Paré MarieÈve,
Maltais François,
Debigaré Richard
Publication year - 2006
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.20.5.lb31-a
Subject(s) - proteolysis , hypoxia (environmental) , myogenesis , muscle atrophy , proteasome , pi3k/akt/mtor pathway , protein kinase b , atrophy , protein degradation , myocyte , reactive oxygen species , medicine , phosphorylation , hyperoxia , endocrinology , ubiquitin , microbiology and biotechnology , chemistry , biology , skeletal muscle , biochemistry , signal transduction , enzyme , lung , gene , oxygen , organic chemistry
Chronic obstructive pulmonary disease is a progressive and irreversible inflammatory disease where peripheral muscle atrophy, present in many subjects, has significant clinical impacts. Factors initiating muscle atrophy are still unknown. Intermittent to chronic hypoxemia is developing as pulmonary status worsen. Indirect evidences connecting hypoxia and muscle proteolysis bring questions deserving to be studied. Hypoxia is able to generate reactive oxygen species (ROS) which can increase the Ubiquitin‐Proteasome system (UPS) activity. We therefore hypothesized that hypoxia, through the production of ROS, would promote muscle atrophy by increasing UPS subunits expression. Methods and results L6 myotubes were exposed to hypoxic (1% O2) or normoxic (21% O2) atmospheres. After 24 hours of hypoxic exposure, we found an up‐regulation of 1.6 and 2.2 times in the mRNA expression level of MuRF‐1 and Atrogin‐1, respectively. In presence of N‐acetyl‐L‐cystein (NAC), we did not observe any increase in MuRF‐1 or Atrogin‐1 mRNAs expression during hypoxia. To confirm the presence of proteolysis, we quantified actin degradation and found a significant accumulation of a 14‐kDa fragment in hypoxic cells. Insulin treatment decreased the 14‐kDa fragment accumulation, suggesting a role for the PI3K/Akt pathway in attenuating proteolysis. Indeed, after 4 hours of hypoxic exposure, decreased Akt phosphorylation was observed. Conclusion Hypoxia has the potential to increase proteolysis and the effect of NAC on MuRF‐1 and Atrogin‐1 mRNA expression suggests that proteolysis is mediated by ROS production. Funding: Local funding