Melatonin Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Autophagy Via an AMPK/mTOR Signaling Pathway
| العنوان: | Melatonin Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Autophagy Via an AMPK/mTOR Signaling Pathway |
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| المؤلفون: | Yang Mu, Yun Dai Chen, Ping Jun Zhu, Qiang Ma, Yuan Sha, Wei Ren Chen, Hongbin Liu |
| المصدر: | Cellular Physiology and Biochemistry, Vol 47, Iss 5, Pp 2067-2076 (2018) |
| بيانات النشر: | S. Karger AG, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | AMPK, 0301 basic medicine, Physiology, Myocardial Reperfusion Injury, Ischemia/reperfusion injury, AMP-Activated Protein Kinases, Pharmacology, lcsh:Physiology, lcsh:Biochemistry, Rats, Sprague-Dawley, Melatonin, 03 medical and health sciences, chemistry.chemical_compound, AMP-activated protein kinase, Autophagy, medicine, Animals, lcsh:QD415-436, PI3K/AKT/mTOR pathway, Evans Blue, lcsh:QP1-981, biology, Chemistry, Myocardium, TOR Serine-Threonine Kinases, medicine.disease, Rats, 030104 developmental biology, mTOR, biology.protein, Signal transduction, Reperfusion injury, Signal Transduction, medicine.drug |
| الوصف: | Background/Aims: Melatonin has been demonstrated to protect cardiac microvascular endothelial cells (CMECs) against ischemia/reperfusion injury (IRI). Autophagy plays different roles in the heart during ischemia and reperfusion. The AMP activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway is associated with autophagy. This study sought to explore whether melatonin regulates CMEC autophagy through the AMPK/mTOR signaling pathway. Methods: The effects of melatonin in IRI were investigated in vivo rat models and in vitro neonatal CMECs. Myocardial infarct size was achieved by Evans blue and triphenyltetrazolium chloride staining. The severity of cell injury was evaluated by cell vitality and lactate dehydrogenase (LDH) release assays, and autophagy was evaluated by transmission electron microscopy and the assessment of autophagy-related gene expression, such as that of Beclin 1 and light chain 3-II. Results: In vivo, melatonin markedly reduced infarcted area, improved cardiac function and decreased LDH release. However, the AMPK activator AICAR and the mTOR inhibitor rapamycin reduced the protective effects of melatonin on IRI. In vitro, Beclin1 and light chain 3-II protein were found to be down-regulated and autophagosomes were found to be reduced in response to melatonin, together with an increase in cell vitality and a decrease in LDH. Treatment with AICAR or rapamycin ablated the benefit observed with melatonin treatment. Conclusions: Melatonin played an important and protective role in CMECs by inhibiting autophagy against IRI via the AMPK/mTOR system. |
| تدمد: | 1421-9778 1015-8987 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ef5210b71e5b9919780bfe8972f80cfc https://doi.org/10.1159/000491474 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ef5210b71e5b9919780bfe8972f80cfc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14219778 10158987 |
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