Modulation of cardiac mitochondrial permeability transition and apoptotic signaling by endurance training and intermittent hypobaric hypoxia

J Magalhães; I O Gonçalves; J Lumini-Oliveira; I Marques-Aleixo; E Passos; S Rocha-Rodrigues; N G Machado; A C Moreira; D Rizo; G Viscor; P J Oliveira; J R Torrella; A Ascensão

doi:10.1016/j.ijcard.2014.02.011

Modulation of cardiac mitochondrial permeability transition and apoptotic signaling by endurance training and intermittent hypobaric hypoxia

Int J Cardiol. 2014 Apr 15;173(1):40-5. doi: 10.1016/j.ijcard.2014.02.011. Epub 2014 Feb 20.

Authors

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

Affiliations

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.

PMID: 24602319
DOI: 10.1016/j.ijcard.2014.02.011

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.

Keywords: Altitude; Apoptosis; Cardioprotection; Oxidative damage; Physical exercise.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / physiology*
Hypoxia / metabolism*
Male
Mitochondria, Heart / physiology*
Mitochondrial Membrane Transport Proteins / physiology*
Mitochondrial Permeability Transition Pore
Oxidative Stress / physiology
Physical Conditioning, Animal / methods
Physical Conditioning, Animal / physiology*
Rats
Rats, Wistar
Signal Transduction / physiology*

Substances

Mitochondrial Membrane Transport Proteins
Mitochondrial Permeability Transition Pore