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Calcium- and ADP-Magnesium-induced respiratory uncoupling in isolated cardiac mitochondria: Influence of cycolsporin A

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Abstract

This study was designed to determine the effect of calcium and ADP-Mg on the oxidative phosphorylation in isolated cardiac mitochondria. The influence of cyclosporin A was also evaluated. The mitochondria were extracted from rat ventricles. Their oxidative phosphorylations were determined in two respiration media with different free Ca2+ concentrations. Respiration was determined with palmitoylcarnitine and either ADP- or ADP-Mg. With elevated free Ca2+concentrations and ADP-Mg, the transition state III to state IV respiration did not occurred. The ADP:O ratio was reduced. The phenomenon was not observed in the other experimental conditions (low free Ca2+ concentration with either ADP- or ADP-Mg or elevated free Ca2+ concentration with ADP-). Uncoupling was allied with a constant AMP production, which maintained an elevated ADP level in the respiration medium and prevented the return to state IV respiration. It was also observed in a respiration medium devoid of free Ca2+ when the mitochondria were pre-loaded with Ca2+. Uncoupling was inhibited by cyclosporin A. Furthermore, the Krebs cycle intermediates released from14C-palmitoylcarnitine oxidation revealed that succinate was increased by elevated free Ca2+ and ADP-Mg. Succinate is a FAD-linked substrate with low respiration efficiency. Its accumulation could account for the decreased ADP:O ratio. The Ca2+- and ADP-Mg-induced uncoupling might be partly responsible for the mechanical abnormalities observed during low-flow ischemia. (Mol Cell Biochem 000: 000-000, 1999)

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Authors and Affiliations

  1. INRA, Unité de Nutrition Lipidique, BV 1540, 17 rue Sully, 21034, Dijon, France

    Emmanuelle Sentex, Alexandra Laurent, Lucie Martine, Stéphane Grégoire & Luc Demaison

  2. LPPCE, Université de Bourgogne, Faculté de Médecine, Dijon Cedex, France

    Luc Rochette

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  1. Emmanuelle Sentex
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  2. Alexandra Laurent
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  3. Lucie Martine
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  4. Stéphane Grégoire
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  5. Luc Rochette
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  6. Luc Demaison
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Sentex, E., Laurent, A., Martine, L. et al. Calcium- and ADP-Magnesium-induced respiratory uncoupling in isolated cardiac mitochondria: Influence of cycolsporin A. Mol Cell Biochem 202, 73–84 (1999). https://doi.org/10.1023/A:1007074330569

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