Modulation of mitochondrial biomarkers by intermittent hypobaric hypoxia and aerobic exercise after eccentric exercise in trained rats

Appl Physiol Nutr Metab. 2017 Jul;42(7):683-693. doi: 10.1139/apnm-2016-0526. Epub 2017 Feb 2.

Abstract

Unaccustomed eccentric contractions induce muscle damage, calcium homeostasis disruption, and mitochondrial alterations. Since exercise and hypoxia are known to modulate mitochondrial function, we aimed to analyze the effects on eccentric exercise-induced muscle damage (EEIMD) in trained rats using 2 recovery protocols based on: (i) intermittent hypobaric hypoxia (IHH) and (ii) IHH followed by exercise. The expression of biomarkers related to mitochondrial biogenesis, dynamics, oxidative stress, and bioenergetics was evaluated. Soleus muscles were excised before (CTRL) and 1, 3, 7, and 14 days after an EEIMD protocol. The following treatments were applied 1 day after the EEIMD: passive normobaric recovery (PNR), 4 h daily exposure to passive IHH at 4000 m (PHR) or IHH exposure followed by aerobic exercise (AHR). Citrate synthase activity was reduced at 7 and 14 days after application of the EEIMD protocol. However, this reduction was attenuated in AHR rats at day 14. PGC-1α and Sirt3 and TOM20 levels had decreased after 1 and 3 days, but the AHR group exhibited increased expression of these proteins, as well as of Tfam, by the end of the protocol. Mfn2 greatly reduced during the first 72 h, but returned to basal levels passively. At day 14, AHR rats had higher levels of Mfn2, OPA1, and Drp1 than PNR animals. Both groups exposed to IHH showed a lower p66shc(ser36)/p66shc ratio than PNR animals, as well as higher complex IV subunit I and ANT levels. These results suggest that IHH positively modulates key mitochondrial aspects after EEIMD, especially when combined with aerobic exercise.

Keywords: biogenèse mitochondriale; biomarqueurs mitochondriaux; dynamique mitochondriale; eccentric exercise; exercice pliométrique; hypoxie intermittente; intermittent hypoxia; lésion musculaire; mitochondrial biogenesis; mitochondrial biomarkers; mitochondrial dynamics; muscle damage.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers / metabolism
  • Citrate (si)-Synthase / metabolism
  • Creatine Kinase / blood
  • Endpoint Determination
  • Energy Metabolism
  • GTP Phosphohydrolases
  • Gene Expression Regulation
  • Hypoxia / metabolism*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Membrane Transport Proteins
  • Mitochondria / metabolism*
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Muscle, Skeletal / metabolism
  • Myoglobin / blood
  • Oxidative Stress
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Physical Conditioning, Animal*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Sirtuins / genetics
  • Sirtuins / metabolism
  • Src Homology 2 Domain-Containing, Transforming Protein 1 / genetics
  • Src Homology 2 Domain-Containing, Transforming Protein 1 / metabolism

Substances

  • Biomarkers
  • Membrane Proteins
  • Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Mitochondrial Proteins
  • Myoglobin
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear
  • SIRT3 protein, rat
  • Shc1 protein, rat
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Tomm20 protein, rat
  • Citrate (si)-Synthase
  • Creatine Kinase
  • Sirtuins
  • GTP Phosphohydrolases
  • Mfn2 protein, rat