Abstract | RATIONALE: OBJECTIVE: METHODS AND RESULTS: Using hypoxia-reoxygenation (H/R) in H9C2 cells, we showed that SIRT3 overexpression prevented CyPD acetylation, limited PTP opening and reduced cell death by 24%. In vitro modification of the CyPD acetylation status in MEFs by site-directed mutagenesis altered capacity of PTP opening by calcium. Calcium Retention Capacity (CRC) was significantly decreased with CyPD-KQ that mimics acetylated protein compared with CyPD WT (871 ± 266 vs 1193 ± 263 nmoles Ca(2+)/mg protein respectively). Cells expressing non-acetylable CyPD mutant (CyPD-KR) displayed 20% decrease in cell death compared to cells expressing CyPD WT after H/R. Correspondingly, in mice we showed that cardiac ischemic postconditioning could not reduce infarct size and CyPD acetylation in SIRT3 KO mice, and was unable to restore CRC in mitochondria as it is observed in WT mice. CONCLUSIONS:
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Authors | T Bochaton, C Crola-Da-Silva, B Pillot, C Villedieu, L Ferreras, M R Alam, H Thibault, M Strina, A Gharib, M Ovize, D Baetz |
Journal | Journal of molecular and cellular cardiology
(J Mol Cell Cardiol)
Vol. 84
Pg. 61-9
(Jul 2015)
ISSN: 1095-8584 [Electronic] England |
PMID | 25871830
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Ltd. All rights reserved. |
Chemical References |
- Cyclophilin D
- Mitochondrial Membrane Transport Proteins
- Mitochondrial Permeability Transition Pore
- PPIF protein, mouse
- Sirtuin 3
- Cyclophilins
- Oxygen
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Topics |
- Acetylation
- Animals
- Cell Death
- Cell Hypoxia
- Cyclophilin D
- Cyclophilins
(metabolism)
- Ischemic Postconditioning
- Male
- Membrane Potential, Mitochondrial
(drug effects)
- Mice, Knockout
- Mitochondrial Membrane Transport Proteins
- Mitochondrial Permeability Transition Pore
- Myocardial Reperfusion Injury
(metabolism)
- Oxygen
(pharmacology)
- Rats
- Sirtuin 3
(metabolism)
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