Differential sensitivity of oxidative and glycolytic muscles to hypoxia-induced muscle atrophy

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Abstract

Hypoxia as a consequence of acute and chronic respiratory disease has been associated with muscle atrophy. This study investigated the sensitivity of oxidative and glycolytic muscles to hypoxia-induced muscle atrophy. Male mice were exposed to 8% normobaric oxygen for up to 21 days. Oxidative soleus and glycolytic extensor digitorum longus (EDL) muscles were isolated, weighed and assayed for gene expression profiles of the ubiquitin-proteasome system (UPS), the autophagy-lysosome pathway (ALP), and glucocorticoid receptor (GR)- and hypoxia-inducible factor-1alpha (HIF1alpha) signaling. Fiber-type composition and the capillary network were investigated. Hypoxia-induced muscle atrophy was more prominent in the EDL than the soleus muscle. Although increased expression of HIF1alpha target genes showed that both muscle types sensed hypoxia, their adaptive responses differed. Atrophy consistently involved a hypoxia-specific effect (i.e. not attributable to a hypoxia-mediated reduction of food intake) in the EDL only. Hypoxia-specific activation of the UPS and ALP and increased expression of the glucocorticoid receptor (Gr) and its target genes were also mainly observed in the EDL. In the soleus, stimulation of gene expression of those pathways could be mimicked to a large extent by food restriction alone. Hypoxia increased the number of capillary contacts per fiber cross-sectional area in both muscles. In the EDL, this was due to type II fiber atrophy, whereas in the soleus the absolute number of capillary contacts increased. These responses represent two distinct modes to improve oxygen supply to muscle fibers, but may aggravate muscle atrophy in COPD patients who have a predominance of type II fibers.
Original languageEnglish
Pages (from-to)200-211
Number of pages12
JournalJournal of Applied Physiology
Volume118
Issue number2
DOIs
Publication statusPublished - 15 Jan 2015

Keywords

  • hypoxia
  • oxidative muscle
  • glycolytic muscle
  • protein-degradation pathways
  • OBSTRUCTIVE PULMONARY-DISEASE
  • SKELETAL-MUSCLE
  • GLUCOCORTICOID-RECEPTOR
  • FIBER-TYPE
  • GLUTAMINE-SYNTHETASE
  • INDUCED ANGIOGENESIS
  • METABOLIC PROFILE
  • HINDLIMB MUSCLES
  • SOLEUS MUSCLE
  • EXPRESSION

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