MiR-219a-2 relieves myocardial ischemia-reperfusion injury by reducing calcium overload and cell apoptosis through HIF1α/ NMDAR pathway
| Autor: | Xi Chen, Shengcun Guo, Shengye Zhang, Fudong Hu, Zheng-ming Jiang, Kui Chen, Xin Fu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Programmed cell death Myocardial Infarction Apoptosis Myocardial Reperfusion Injury Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Western blot medicine Animals Myocytes Cardiac Receptor Hypoxia Evans Blue medicine.diagnostic_test Myocardium Cell Biology medicine.disease Cell Hypoxia Cell biology Mice Inbred C57BL MicroRNAs 030104 developmental biology chemistry 030220 oncology & carcinogenesis NMDA receptor Calcium Reperfusion injury Intracellular Signal Transduction |
| Zdroj: | Experimental cell research. 395(1) |
| ISSN: | 1090-2422 |
| Popis: | Objective During the process of myocardial ischemia-reperfusion injury (MIRI), the intracellular Ca2+ concentration ([Ca2+]i) continues to increase, leads to the cardiomyocyte apoptosis and eventually causes myocardial damage, while the upstream regulation mechanism of calcium overload is still unknown. This study focuses on the role of miR-219a-2 in MIRI and aims to elaborate its regulatory mechanism on calcium overload that occurs during MIRI. Methods The expression of miR-219a-2 was determined in the heart tissues of MIRI mice by qRT-PCR. The [Ca2+]i was measured by fluo-3 using a fluorescence microplate reader. The expression of hypoxiainducible factor 1α (HIF1α) and NR1, the obligatory subunit of N-methyl- d -aspartate receptor 1 (NMDAR), were measured by qRT-PCR and western blot. The luciferase reporter assay was used to confirm the interplay between miR-219a-2 and HIF1α and the interplay between HIF1α and NR1. The cell apoptosis was measured by the expression level of B-cell lymphoma 2 interacting mediator of cell death (Bim) and the number of TUNEL-positive cells. The myocardial infarct size of mice was measured by TTC/Evans Blue staining. Results MiR-219a-2 was down-regulated in the heart tissues of MIRI mice. miR-219a-2 overexpression decreased [Ca2+]i and the expression of HIF1α and NR1 in hypoxia/reoxygenation (H/R)-treated HL-1 cells. Then, the luciferase reporter assay showed that miR-219a-2 inhibited the transcription of HIF1α and HIF1α promoted the transcription of NR1. Both HIF1α overexpression and NMDAR function enhancement removed the inhibitory effect of miR-219a-2 on calcium overload and cell apoptosis in H/R-treated HL-1 cells. Finally, the overexpression of miR-219a-2 decreased Ca2+ concentration, cell apoptosis, and myocardial infarction size in MIRI mice, while the NMDAR function enhancer reversed the therapeutic effect of miR-219a-2. Conclusion MiR-219a-2 reducing NMDAR-mediated calcium overload via HIF1α/NR1 axis, thus alleviating cell apoptosis in MIRI. |
| Databáze: | OpenAIRE |
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