title: Modulation of cardiac mitochondrial permeability transition and apoptotic signaling by endurance training and intermittent hypobaric hypoxia.
abstract: BACKGROUND
  Modulation of the mitochondrial permeability transition pore (MPTP) and inhibition of the apoptotic signaling are critically associated with the cardioprotective phenotypes afforded by both intermittent hypobaric-hypoxia (IHH) and endurance-training (ET). We recently proposed that IHH and ET improve cardiac function and basic mitochondrial capacity, although without showing addictive effects. Here we investigate whether a combination of IHH and ET alters cardiac mitochondrial vulnerability to MPTP and related apoptotic signaling.
  
  
  METHODS
  Male Wistar rats were divided into normoxic-sedentary (NS), normoxic-exercised (NE, 1h/day/5 week treadmill-running), hypoxic-sedentary (HS, 6000 m, 5h/day/5 weeks) and hypoxic-exercised (HE) to study susceptibility to calcium-induced cardiac MPTP opening. Mitochondrial cyclophilin D (CypD), adenine nucleotide translocator (ANT), Bax and Bcl-2 protein contents were semi-quantified by Western blotting. Cardiac caspase 3-, 8- and 9-like activities were measured. Mitochondrial aconitase and superoxide dismutase (MnSOD) activity and malondialdehyde (MDA) and sulphydryl group (-SH) content were determined.
  
  
  RESULTS
  Susceptibility to MPTP decreased in NE and HS vs. NS and even further in HE. The ANT content increased in HE vs. NS. Bcl-2/Bax ratio increased in NE and HS compared to NS. Decreased activities in tissue caspase 3-like (HE vs. NS) and caspase 9-like (HS and HE vs. NS) were observed. Mitochondrial aconitase increased in NE and HS vs. NS. No alterations between groups were observed for caspase 8-like activity, MnSOD, CypD, MDA and -SH.
  
  
  CONCLUSIONS
  Data confirm that IHH and ET modulate cardiac mitochondria to a protective phenotype characterized by decreased MPTP induction and apoptotic signaling, although without visible addictive effects as initially hypothesized.
authors.affiliation: Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal. Electronic address: jmaga@fade.up.pt.
authors.forename: J
authors.initials: J
authors.lastname: Magalhães
authors.affiliation: Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors.forename: I O
authors.initials: IO
authors.lastname: Gonçalves
authors.affiliation: Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal; Faculty of Health Sciences, University of Fernando Pessoa, Portugal.
authors.forename: J
authors.initials: J
authors.lastname: Lumini-Oliveira
authors.affiliation: Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors.forename: I
authors.initials: I
authors.lastname: Marques-Aleixo
authors.affiliation: Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors.forename: E
authors.initials: E
authors.lastname: Passos
authors.affiliation: Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors.forename: S
authors.initials: S
authors.lastname: Rocha-Rodrigues
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal.
authors.forename: N G
authors.initials: NG
authors.lastname: Machado
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal.
authors.forename: A C
authors.initials: AC
authors.lastname: Moreira
authors.affiliation: Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Rizo
authors.affiliation: Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Viscor
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal.
authors.forename: P J
authors.initials: PJ
authors.lastname: Oliveira
authors.affiliation: Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Spain.
authors.forename: J R
authors.initials: JR
authors.lastname: Torrella
authors.affiliation: Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Ascensão
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000379:methods / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore
keywords: Altitude; Apoptosis; Cardioprotection; Oxidative damage; Physical exercise