| Acute exercise protects against calcium-induced cardiac mitochondrial permeability transition pore opening in doxorubicin-treated rats. | |
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MedLine Citation:
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PMID: 20666733 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The use of DOX (doxorubicin), an antibiotic used in oncological treatments, is limited by a dose-related cardiotoxicity against which acute exercise is protective. However, the mitochondrial-related mechanisms of this protection remain unknown. Therefore the present study aimed to determine the effects of an acute endurance exercise bout performed 24 h before DOX treatment on heart and liver mitochondrial function. A total of 20 adult male Wistar rats were divided into groups as follows: non-exercised with saline (NE + SAL), non-exercised DOX-treated (NE + DOX), exercised with saline (EX + SAL) and exercised DOX-treated (EX + DOX). The animals performed a 60 min exercise bout on a treadmill or remained sedentary 24 h before receiving either a DOX bolus (20 mg/kg of body weight) or saline. Heart and liver mitochondrial function [oxygen consumption, membrane potential (DeltaPsi) and cyclosporin-A-sensitive calcium-induced MPTP (mitochondrial permeability transition pore) opening] were evaluated. The activities of the respiratory complex, Mn-SOD (superoxide dismutase), caspases 3 and 9, as well as the levels of ANT (adenine nucleotide translocase), VDAC (voltage-dependent anion channel), CypD (cyclophilin D), Bax and Bcl-2, were measured. Acute exercise prevented the decreased cardiac mitochondrial function (state 3, phosphorylative lagphase; maximal DeltaPsi generated both with complex I- and II-linked substrates and calcium-induced MPTP opening) induced by DOX treatment. Exercise also prevented the DOX-induced decreased activity of cardiac mitochondrial chain complexes I and V, and increased caspase 3 and 9 activities. DOX administration and exercise caused increased cardiac mitochondrial SOD activity. Exercise ameliorated liver mitochondrial complex activities. No alterations were observed in the measured MPTP and apoptosis-related proteins in heart and liver mitochondria. The results demonstrate that acute exercise protects against cardiac mitochondrial dysfunction, preserving mitochondrial phosphorylation capacity and attenuating DOX-induced decreased tolerance to MPTP opening. |
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Authors:
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António Ascensão; José Lumini-Oliveira; Nuno G Machado; Rita M Ferreira; Inês O Gonçalves; Ana C Moreira; Franklin Marques; Vilma A Sardão; Paulo J Oliveira; José Magalhães |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Clinical science (London, England : 1979) Volume: 120 ISSN: 1470-8736 ISO Abbreviation: Clin. Sci. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-09-22 Completed Date: 2010-11-23 Revised Date: 2011-05-05 |
Medline Journal Info:
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Nlm Unique ID: 7905731 Medline TA: Clin Sci (Lond) Country: England |
Other Details:
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Languages: eng Pagination: 37-49 Citation Subset: IM |
Affiliation:
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Research Centre in Physical Activity, Health and Leisure, Faculty of Sport Sciences, University of Porto, 4200-450 Porto, Portugal. aascensao@fcdef.up.pt |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibiotics, Antineoplastic / pharmacology* Apoptosis / drug effects, physiology Calcium / metabolism, physiology Doxorubicin / pharmacology* Male Mitochondria, Heart / drug effects*, metabolism, physiology Mitochondria, Liver / drug effects, metabolism, physiology Mitochondrial Membrane Transport Proteins / metabolism* Motor Activity / physiology* Oxygen Consumption / drug effects, physiology Proton Pumps / metabolism Rats Rats, Wistar Signal Transduction / drug effects, physiology Superoxide Dismutase / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antineoplastic; 0/Mitochondrial Membrane Transport Proteins; 0/Proton Pumps; 0/mitochondrial permeability transition pore; 23214-92-8/Doxorubicin; 7440-70-2/Calcium; EC 1.15.1.1/Superoxide Dismutase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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