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Abstract:
BACKGROUND:MicroRNAs (miRNAs) are involved in myocardial ischemia-reperfusion injury. miRNA-421 (miR-421) plays a significant role in the initiation of apoptosis and myocardial infarction. However, the molecular regulation of miR-421 in myocardial ischemia-reperfusion injury requires further elucidation. METHODS:An in vitro hypoxia/reoxygenation model was established, and the expression levels of miR-421 and Sirtuin-3 (Sirt3) in H9c2 cells were quantified using quantitative real-time polymerase chain reaction. Flow cytometry was employed to measure the effects of miR-421 on myocardial apoptosis induced by hypoxia/reoxygenation. The activity of lactate dehydrogenase and superoxide dismutase and levels of malondialdehyde were measured. The binding sites of miR-421 on Sirt3 were predicted using TargetScan software. A luciferase reporter assay was used to validate the direct targeting of Sirt3 with miR-421. Protein expression levels of Sirt3 and its downstream proteins were evaluated using Western blot analysis. RESULTS:Exposure of H9c2 cells to hypoxia/reoxygenation led to increased apoptosis, levels of malondialdehyde and lactate dehydrogenase, and decreased levels of superoxide dismutase. miR-421 knockdown resulted in decreased apoptosis, levels of lactate dehydrogenase and malondialdehyde, and increased superoxide dismutase levels in H9c2 cells. Hypoxia/reoxygenation significantly decreased the relative expression levels of Sirt3. Down-regulation of Sirt3 resulted from overexpression of miR-421, which directly targeted Sirt3. Knockdown of miR-421 up-regulated Sirt3 expression, inhibited activation of the Jun N-terminal kinase/activator protein 1 pathway and caspase 9/3-dependent cell death. CONCLUSION:The miR-421-Sirt3-Jun N-terminal kinase/activator protein 1 axis is a novel molecular mechanism that accommodates hypoxia/reoxygenation-induced oxidative stress and apoptosis and provides a new direction for the study and treatment of hypoxia/reoxygenation.
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最新影响因子:1.581 | 期刊ISSN:0267-6591 | CiteScore: |
出版周期:Bimonthly | 是否OA:YES | 出版年份:1986 |
期刊官方网址:http://prf.sagepub.com/
期刊投稿地址:http://www.sagepub.com/journals/Journal201824/manuscriptSubmission
自引率:13.30% | 研究方向:医学-外周血管病 |
出版地区:ENGLAND |
SCI期刊coverage:Science Citation Index Expanded(科学引文索引扩展)
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Published by Sage Publications. ISSN (printed): 0267-6591. ISSN (electronic): 1477-111X. Perfusion provides current information on all aspects of perfusion, oxygenation and biocompatibility and their use
由Sage出版社出版。ISSN(印刷):0267 - 6591。ISSN(电子):1477 - 111 x。 灌注提供灌注、氧合、生物相容性及其应用的最新信息
大类(学科) | 小类(学科) | 学科排名 |
医学 |
CARDIAC & CARDIOVASCULAR SYSTEMS (心脏和心血管系统) 4区 PERIPHERAL VASCULAR DISEASE (外周血管病) 4区 |
112/128 62/65 |
年度总发文量 | 年度论文发表量 | 年度综述发表量 |
100 | 95 | 5 |
引文计数(2018)
文献(2015-2017)
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研究方向:AGRONOMY-GENETICS & HEREDITY
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研究方向:农林科学-林学
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研究方向:INFECTIOUS DISEASES-PARASITOLOGY
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研究方向:PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH-INFECT
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研究方向:医学-热带医学
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研究方向:医学-公共卫生、环境卫生与职业卫生
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研究方向:医学-公共卫生、环境卫生与职业卫生
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