title: Fifteen days of 3,200 m simulated hypoxia marginally regulates markers for protein synthesis and degradation in human skeletal muscle.
abstract: Chronic hypoxia leads to muscle atrophy. The molecular mechanisms responsible for this phenomenon are not well defined in vivo. We sought to determine how chronic hypoxia regulates molecular markers of protein synthesis and degradation in human skeletal muscle and whether these regulations were related to the regulation of the hypoxia-inducible factor (HIF) pathway. Eight young male subjects lived in a normobaric hypoxic hotel (FiO214.1%, 3,200 m) for 15 days in well-controlled conditions for nutrition and physical activity. Skeletal muscle biopsies were obtained in the musculus vastus lateralis before (PRE) and immediately after (POST) hypoxic exposure. Intramuscular hypoxia-inducible factor-1 alpha (HIF-1α) protein expression decreased (-49%,P=0.03), whereas hypoxia-inducible factor-2 alpha (HIF-2α) remained unaffected from PRE to POST hypoxic exposure. Also, downstream HIF-1α target genesVEGF-A(-66%,P=0.006) andBNIP3(-24%,P=0.002) were downregulated, and a tendency was measured for neural precursor cell expressed, developmentallyNedd4(-47%,P=0.07), suggesting lowered HIF-1α transcriptional activity after 15 days of exposure to environmental hypoxia. No difference was found on microtubule-associated protein 1 light chain 3 type II/I (LC3b-II/I) ratio, and P62 protein expression tended to increase (+45%,P=0.07) compared to PRE exposure levels, suggesting that autophagy was not modulated after chronic hypoxia. The mammalian target of rapamycin complex 1 pathway was not altered as Akt, mammalian target of rapamycin, S6 kinase 1, and 4E-binding protein 1 phosphorylation did not change between PRE and POST. Finally, myofiber cross-sectional area was unchanged between PRE and POST. In summary, our data indicate that moderate chronic hypoxia differentially regulates HIF-1α and HIF-2α, marginally affects markers of protein degradation, and does not modify markers of protein synthesis or myofiber cross-sectional area in human skeletal muscle.
authors: Department of Kinesiology, Exercise Physiology Research Group, FaBeR, KU Leuven, Leuven, Belgium.
authors: Gommaar
authors: G
authors: D'Hulst
authors: Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, Australia; Department of Health Sciences, University of Milano-Bicocca, Monza, Italy.
authors: Alessandra
authors: A
authors: Ferri
authors: Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve.
authors: Damien
authors: D
authors: Naslain
authors: Institut de Recherche Expérimentale et Clinique, Pôle de Recherche Cardiovasculaire, Université catholique de Louvain, Brussels, Belgium.
authors: Luc
authors: L
authors: Bertrand
authors: Institut de Recherche Expérimentale et Clinique, Pôle de Recherche Cardiovasculaire, Université catholique de Louvain, Brussels, Belgium.
authors: Sandrine
authors: S
authors: Horman
authors: Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve.
authors: Marc
authors: M
authors: Francaux
authors: Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, Australia.
authors: David J
authors: DJ
authors: Bishop
authors: Department of Kinesiology, Exercise Physiology Research Group, FaBeR, KU Leuven, Leuven, Belgium; Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve.
authors: Louise
authors: L
authors: Deldicque
keywords: HIF-1α; autophagy; hypoxia; mTORC1