J Magalhães1, I O Gonçalves2, J Lumini-Oliveira3, I Marques-Aleixo2, E Passos2, S Rocha-Rodrigues2, N G Machado4, A C Moreira4, D Rizo5, G Viscor5, P J Oliveira4, J R Torrella5, A Ascensão2. 1. Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal. Electronic address: jmaga@fade.up.pt. 2. Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal. 3. Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal; Faculty of Health Sciences, University of Fernando Pessoa, Portugal. 4. CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Portugal. 5. Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, Spain.
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.
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: Robert T Mallet; Eugenia B Manukhina; Steven Shea Ruelas; James L Caffrey; H Fred Downey Journal: Am J Physiol Heart Circ Physiol Date: 2018-04-13 Impact factor: 4.733
Authors: Emilio A Herrera; Jorge G Farías; Alejandro González-Candia; Stefania E Short; Catalina Carrasco-Pozo; Rodrigo L Castillo Journal: Mar Drugs Date: 2015-02-04 Impact factor: 5.118
Authors: David Rizo-Roca; Jèssica B Bonet; Büsra Ínal; Juan Gabriel Ríos-Kristjánsson; Teresa Pagès; Ginés Viscor; Joan R Torrella Journal: Front Physiol Date: 2018-05-04 Impact factor: 4.566
Authors: Ginés Viscor; Joan R Torrella; Luisa Corral; Antoni Ricart; Casimiro Javierre; Teresa Pages; Josep L Ventura Journal: Front Physiol Date: 2018-07-09 Impact factor: 4.566