title: Differential sensitivity of oxidative and glycolytic muscles to hypoxia-induced muscle atrophy.
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 expression profiles of the ubiquitin-proteasome system (UPS), the autophagy-lysosome pathway (ALP), and glucocorticoid receptor (GR) and hypoxia-inducible factor-1α (HIF1α) 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 HIF1α 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 chronic obstructive pulmonary disease patients who have a predominance of type II fibers.
authors.affiliation: NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands; Department of Anatomy and Embryology, Maastricht University Medical Center+, Maastricht, The Netherlands; and.
authors.forename: C C
authors.initials: CC
authors.lastname: de Theije
authors.affiliation: NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands; Department of Respiratory Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: R C J
authors.initials: RC
authors.lastname: Langen
authors.affiliation: NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands; Department of Anatomy and Embryology, Maastricht University Medical Center+, Maastricht, The Netherlands; and.
authors.forename: W H
authors.initials: WH
authors.lastname: Lamers
authors.affiliation: NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands; Department of Respiratory Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: H R
authors.initials: HR
authors.lastname: Gosker
authors.affiliation: NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands; Department of Respiratory Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: A M W J
authors.initials: AM
authors.lastname: Schols
authors.affiliation: NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands; Department of Anatomy and Embryology, Maastricht University Medical Center+, Maastricht, The Netherlands; and leo.koehler@maastrichtuniversity.nl.
authors.forename: S E
authors.initials: SE
authors.lastname: Köhler
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001343:Autophagy; D015870:Gene Expression; D005938:Glucocorticoids / Q000378:metabolism; D006019:Glycolysis; D000860:Hypoxia / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000209:etiology / Q000473:pathology*; D010084:Oxidation-Reduction; D011897:Random Allocation; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D044767:Ubiquitin-Protein Ligases
keywords: glycolytic muscle; hypoxia; oxidative muscle; protein-degradation pathways