Inhibiting Mitochondrial Fission Protects the Heart Against Ischemia/Reperfusion Injury
| العنوان: | Inhibiting Mitochondrial Fission Protects the Heart Against Ischemia/Reperfusion Injury |
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| المؤلفون: | Sang Bing Ong, Shiang Y. Lim, Sapna Subrayan, Derek M. Yellon, Derek J. Hausenloy, Sean M. Davidson |
| المصدر: | Circulation. 121:2012-2022 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Dynamins, Male, Pathology, medicine.medical_specialty, Cardiotonic Agents, Green Fluorescent Proteins, Ischemia, Myocardial Reperfusion Injury, Pharmacology, Transfection, Membrane Fusion, Cell Line, GTP Phosphohydrolases, Mice, DNM1L, Mitofusin-2, Physiology (medical), medicine, Animals, Myocytes, Cardiac, Quinazolinones, Microscopy, Confocal, Cell Death, business.industry, Age Factors, Hypoxia (medical), medicine.disease, Mitochondria, Cardiovascular physiology, Mice, Inbred C57BL, Microscopy, Electron, Apoptosis, Mitochondrial Membranes, Mitochondrial fission, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Microtubule-Associated Proteins, Reperfusion injury |
| الوصف: | Background— Whether alterations in mitochondrial morphology affect the susceptibility of the heart to ischemia/reperfusion injury is unknown. We hypothesized that modulating mitochondrial morphology protects the heart against ischemia/reperfusion injury. Methods and Results— In response to ischemia, mitochondria in HL-1 cells (a cardiac-derived cell line) undergo fragmentation, a process that is dependent on the mitochondrial fission protein dynamin-related protein 1 (Drp1). Transfection of HL-1 cells with the mitochondrial fusion proteins mitofusin 1 or 2 or with Drp1 K38A , a dominant-negative mutant form of Drp1, increased the percentage of cells containing elongated mitochondria (65±4%, 69±5%, and 63±6%, respectively, versus 46±6% in control: n=80 cells per group; P P P P =0.023). Finally, treatment of adult murine cardiomyocytes with mitochondrial division inhibitor-1 reduced cell death and inhibited mitochondrial permeability transition pore opening after simulated ischemia/reperfusion injury, and in vivo treatment with mitochondrial division inhibitor-1 reduced myocardial infarct size in mice subject to coronary artery occlusion and reperfusion (21.0±2.2% with mitochondrial division inhibitor-1 versus 48.0±4.5% in control; n=6 animals per group; P Conclusion— Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury, suggesting a novel pharmacological strategy for cardioprotection. |
| تدمد: | 1524-4539 0009-7322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7bc6a78c5e024b548297535f5960461eTest https://doi.org/10.1161/circulationaha.109.906610Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7bc6a78c5e024b548297535f5960461e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244539 00097322 |
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