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: Evi Masschelein, Ruud Van Thienen, Gommaar D'Hulst, Peter Hespel, Martine Thomis, Louise Deldicque
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 28 Issue 2 Pg. 1022-34 (Feb 2014) ISSN: 1530-6860 [Electronic] United States
• PMID: 24200883 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Twin Study)

Chemical References

• BNIP3 protein, human
• DDIT4 protein, human
• MAP1LC3A protein, human
• Membrane Proteins
• Microtubule-Associated Proteins
• Muscle Proteins
• Proto-Oncogene Proteins
• Transcription Factors
• FBXO32 protein, human
• SKP Cullin F-Box Protein Ligases

Topics

• Adult
• Autophagy (physiology)
• Blotting, Western
• Exercise (physiology)
• Genotype
• Humans
• Hypoxia (physiopathology)
• Membrane Proteins (genetics, metabolism)
• Microtubule-Associated Proteins (genetics, metabolism)
• Muscle Proteins (genetics, metabolism)
• Proto-Oncogene Proteins (genetics, metabolism)
• SKP Cullin F-Box Protein Ligases (genetics, metabolism)
• Transcription Factors (genetics, metabolism)
• Young Adult