title: Acute environmental hypoxia induces LC3 lipidation in a genotype-dependent manner.
abstract: Hypoxia-induced muscle wasting is a phenomenon often described with prolonged stays at high altitude, which has been attributed to altered protein metabolism. We hypothesized that acute normobaric hypoxia would induce a negative net protein balance by repressing anabolic and activating proteolytic signaling pathways at rest and postexercise and that those changes could be partially genetically determined. Eleven monozygotic twins participated in an experimental trial in normoxia and hypoxia (10.7% O2). Muscle biopsy samples were obtained before and after a 20-min moderate cycling exercise. In hypoxia at rest, autophagic flux was increased, as indicated by an increased microtubule-associated protein 1 light chain 3 type II/I (LC3-II/I) ratio (+25%) and LC3-II expression (+60%) and decreased p62/SQSTM1 expression (-25%; P<0.05), whereas exercise reversed those changes to a level similar to that with normoxia except for p62/SQSTM1, which was further decreased (P<0.05). Hypoxia also increased Bnip3 (+34%) and MAFbx (+18%) mRNA levels as well as REDD1 expression (+439%) and AMP-activated protein kinase phosphorylation (+22%; P<0.05). Among the molecular responses to hypoxia and/or exercise, high monozygotic similarity was found for REDD1, LC3-II, and LC3-II/I (P<0.05). Our results indicate that environmental hypoxia modulates protein metabolism at rest and after moderate exercise by primarily increasing markers of protein breakdown and, more specifically, markers of the autophagy-lysosomal system, with a modest genetic contribution.
authors.affiliation: 1Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Tervuursevest 101, B-3001 Leuven, Belgium. louise.deldicque@faber.kuleuven.be.
authors.forename: Evi
authors.initials: E
authors.lastname: Masschelein
authors.forename: Ruud
authors.initials: R
authors.lastname: Van Thienen
authors.forename: Gommaar
authors.initials: G
authors.lastname: D'Hulst
authors.forename: Peter
authors.initials: P
authors.lastname: Hespel
authors.forename: Martine
authors.initials: M
authors.lastname: Thomis
authors.forename: Louise
authors.initials: L
authors.lastname: Deldicque
mesh_terms: D000328:Adult; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D015444:Exercise / Q000502:physiology; D005838:Genotype; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: C090121:BNIP3 protein, human; C469991:DDIT4 protein, human; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009124:Muscle Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases
keywords: autophagy; exercise; monozygotic twin design; p62