Roberto Carlos Nava1,2,3, Zachary McKenna4, Zachary Fennel4, Quint Berkemeier4, Jeremy Ducharme4, Flávio de Castro Magalhães4,5, Fabiano Trigueiro Amorim4, Christine Mermier4. 1. Department of Health, Exercise, and Sports Sciences, University of New Mexico, Albuquerque, NM, USA. roberto.nava@joslin.harvard.edu. 2. Research Division, Joslin Diabetes Center, Boston, MA, USA. roberto.nava@joslin.harvard.edu. 3. Harvard Medical School, Harvard University, Boston, MA, USA. roberto.nava@joslin.harvard.edu. 4. Department of Health, Exercise, and Sports Sciences, University of New Mexico, Albuquerque, NM, USA. 5. Department of Physical Education, Federal University of Jequitinhonha and Mucuri Valleys (UFVJM), Diamantina, Brazil.
Abstract
PURPOSE: Our aim was to determine the effect of repeated sprint exercise in hypoxia on HIF-1 and HIF-1-regulated genes involved in glycolysis, mitochondrial turnover and oxygen transport. We also determined whether genes upregulated by exercise in hypoxia were dependent on the activation of HIF-1 in an in vitro model of exercise in hypoxia. METHODS: Eight endurance athletes performed bouts of repeated sprint exercise in control and hypoxic conditions. Skeletal muscle was sampled pre, post and 3 h post-exercise. HIF-1α protein and HIF1A, PDK1, GLUT4, VEGFA, BNIP3, PINK1 and PGC1A mRNA were measured. C2C12 myotubes were exposed to hypoxia and muscle contraction following treatment with a HIF-1α inhibitor to determine whether hypoxia-sensitive gene expression was dependent on HIF-1α. RESULTS: Sprint exercise in hypoxia increased HIF-1α protein expression immediately post-exercise [fold change (FC) = 3.5 ± 2.0]. Gene expression of PDK1 (FC = 2.1 ± 1.2), BNIP3 (FC = 2.4 ± 1.4) and VEGFA (FC = 2.7 ± 1.7) increased 3 h post-exercise in hypoxia but not control. PGC1A mRNA increased 3 h post-exercise in control (FC = 5.16) and hypoxia (FC = 5.7 ± 4.1) but there was no difference between the trials. Results from the in vitro experiment showed that hypoxia plus contraction also increased PDK1, BNIP3, and VEGFA gene expression. These responses were inhibited when HIF-1 protein activity was suppressed. CONCLUSION: Repeated sprint exercise in hypoxia upregulates some genes involved in glycolytic metabolism, mitochondrial turnover, and oxygen transport. HIF-1α is necessary for the expression of these genes in skeletal muscle cells.
PURPOSE: Our aim was to determine the effect of repeated sprint exercise in hypoxia on HIF-1 and HIF-1-regulated genes involved in glycolysis, mitochondrial turnover and oxygen transport. We also determined whether genes upregulated by exercise in hypoxia were dependent on the activation of HIF-1 in an in vitro model of exercise in hypoxia. METHODS: Eight endurance athletes performed bouts of repeated sprint exercise in control and hypoxic conditions. Skeletal muscle was sampled pre, post and 3 h post-exercise. HIF-1α protein and HIF1A, PDK1, GLUT4, VEGFA, BNIP3, PINK1 and PGC1A mRNA were measured. C2C12 myotubes were exposed to hypoxia and muscle contraction following treatment with a HIF-1α inhibitor to determine whether hypoxia-sensitive gene expression was dependent on HIF-1α. RESULTS: Sprint exercise in hypoxia increased HIF-1α protein expression immediately post-exercise [fold change (FC) = 3.5 ± 2.0]. Gene expression of PDK1 (FC = 2.1 ± 1.2), BNIP3 (FC = 2.4 ± 1.4) and VEGFA (FC = 2.7 ± 1.7) increased 3 h post-exercise in hypoxia but not control. PGC1A mRNA increased 3 h post-exercise in control (FC = 5.16) and hypoxia (FC = 5.7 ± 4.1) but there was no difference between the trials. Results from the in vitro experiment showed that hypoxia plus contraction also increased PDK1, BNIP3, and VEGFA gene expression. These responses were inhibited when HIF-1 protein activity was suppressed. CONCLUSION: Repeated sprint exercise in hypoxia upregulates some genes involved in glycolytic metabolism, mitochondrial turnover, and oxygen transport. HIF-1α is necessary for the expression of these genes in skeletal muscle cells.