Mitochondrial fusion promoter restores mitochondrial dynamics balance and ameliorates diabetic cardiomyopathy in an optic atrophy 1‐dependent way
| العنوان: | Mitochondrial fusion promoter restores mitochondrial dynamics balance and ameliorates diabetic cardiomyopathy in an optic atrophy 1‐dependent way |
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| المؤلفون: | Junjun Kang, Ke Zeng, Mingzhe Yu, Feng Fu, Chaoyang Liu, Rui Shi, Mantian Mi, Mingge Ding |
| المصدر: | Acta Physiologica. 229 |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Diabetic Cardiomyopathies, Physiology, 030204 cardiovascular system & hematology, medicine.disease_cause, Membrane Fusion, Mitochondrial Dynamics, Diabetes Mellitus, Experimental, GTP Phosphohydrolases, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Downregulation and upregulation, Diabetic cardiomyopathy, Diabetes mellitus, Internal medicine, medicine, Animals, Superoxide, Intracellular Membranes, medicine.disease, Streptozotocin, Rats, 030104 developmental biology, Endocrinology, mitochondrial fusion, chemistry, Optic Atrophy 1, Oxidative stress, medicine.drug |
| الوصف: | Aim Imbalanced mitochondrial dynamics including suppressed mitochondrial fusion has been observed in diabetic hearts. However, it is still unknown whether mitochondrial fusion promoter is an effective protection to diabetic hearts. This study was designed to explore the efficacy of mitochondrial fusion promoter on diabetic cardiomyopathy (DCM). Methods Male Sprague-Dawley rats were injected with streptozotocin (STZ, 65 mg/kg/d) intraperitoneally to induce diabetes. Seven weeks after vehicle or STZ injection, control or diabetic rats were treated with the vehicle or a mitochondrial fusion promoter-M1 (2 mg/kg/d) intraperitoneally for 6 weeks. Moreover, M1 was administrated to the primary cardiomyocytes cultured in normal glucose medium (NG, 5.5 mmol/L) or high glucose (HG, 33 mnol/L). Results Administration of M1 significantly promoted mitochondrial fusion and attenuated the reduction in optic atrophy 1 (Opa1) expression in diabetic hearts. Importantly, M1 treatment attenuated oxidative stress, improved mitochondrial function and alleviated DCM in diabetic rats. In HG-treated cardiomyocytes, M1 treatment consistently increased the expression of Opa1, promoted mitochondrial fusion, enhanced mitochondrial respiratory capacity and reduced mitochondria-derived superoxide production, all of which were blunted by Opa1 siRNA knockdown. In addition, selective upregulation of Opa1 alone can also promote mitochondrial fusion, improve mitochondrial function and inhibit mitochondria-derived superoxide production in HG-cultured cardiomyocytes. Conclusion Our findings show for the first time that mitochondrial fusion promoter M1 effectively balances mitochondrial dynamics and protects against diabetic cardiomyopathy (DCM) via an Opa1-dependent way, suggesting that promoting mitochondrial fusion might be a potential therapeutic strategy for DCM. |
| تدمد: | 1748-1716 1748-1708 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ffe1df0dc52f5bb21407559f3f8b1f46Test https://doi.org/10.1111/apha.13428Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....ffe1df0dc52f5bb21407559f3f8b1f46 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17481716 17481708 |
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