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

被引:31
|
作者
Magalhaes, J. [1 ]
Goncalves, I. O. [1 ]
Lumini-Oliveira, J. [1 ,2 ]
Marques-Aleixo, I. [1 ]
Passos, E. [1 ]
Rocha-Rodrigues, S. [1 ]
Machado, N. G. [3 ]
Moreira, A. C. [3 ]
Rizo, D. [4 ]
Viscor, G. [4 ]
Oliveira, P. J. [3 ]
Torrella, J. R. [4 ]
Ascensao, A. [1 ]
机构
[1] Univ Porto, Fac Sport, Res Ctr Phys Act Hlth & Leisure, P-4200450 Oporto, Portugal
[2] Univ Fernando Pessoa, Fac Hlth Sci, Oporto, Portugal
[3] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, P-3000 Coimbra, Portugal
[4] Univ Barcelona, Fac Biol, Dept Physiol & Immunol, E-08007 Barcelona, Spain
关键词
Physical exercise; Altitude; Cardioprotection; Oxidative damage; Apoptosis; EXERCISE-INDUCED CARDIOPROTECTION; UP-REGULATION; HEART-MITOCHONDRIA; OXIDATIVE STRESS; PORE; SUSCEPTIBILITY; RESPIRATION; ADAPTATION; EXPRESSION; INCREASES;
D O I
10.1016/j.ijcard.2014.02.011
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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, 1 h/day/5 week treadmill-running), hypoxic-sedentary (HS, 6000 m, 5 h/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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:40 / 45
页数:6
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