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MicroRNA-410 is involved in mitophagy after cardiac ischemia/reperfusion injury by targeting high-mobility group box 1 protein.

Abstract：

:Mitochondrial dysfunction has emerged as a critical pathophysiological factor of myocardial ischemia/reperfusion (I/R) injury. A thorough understanding of mitochondrial dysfunction during I/R at the molecular level is urgently needed. One prominent microRNA, miR-410, was previously reported to be dynamically regulated in diverse cardiomyopathies, but its mechanism is unclear. In the present study, in a cardiac I/R injury mice model, the expression of miR-410 was significantly upregulated, accompanied with decreased mitochondrial function and mitophagy deficit. After an unbiased search for downstream messenger RNA targets of miR-410, effects of the target gene in mitochondrial dysfunction during I/R injury and the underlying mechanism were further explored in cultured human adult cardiac myocytes (HACMs). The results showed that MitoTracker Red-labeled HACMs mitochondria overlapped with GFP-LC3-labeled autophagosomes, suggesting the presence of mitophagy. MiR-410 expression was significantly increased in hypoxia/reoxygenation (H/R)-stimulated HACMs. MiR-410 overexpression further inhibited cell viability, ATP production, mitochondrial membrane potential and mitophagy level, and increased caspase-3 activity, Bax expression and cytochrome c release. Conversely, inhibition of miR-410 attenuated these effects. We found that miR-410 directly interacted with the 3'-untranslated region of the suppressor of high-mobility group box 1 protein (HMGB1) by Dual-Luciferase assay. Moreover, pcDNA3.1-HMGB1 pretreatment effectively reduced the inhibition effects of cell viability and mitophagy brought by H/R, while all those effects can be attenuated by pretreatment with HSPB1 siRNA transfection. Taken together, our results suggest that miR-410 may inhibit mitophagy after cardiac I/R injury by modulating HSPB1 activity via directly targeting HMGB1.

journal_name

J Cell Biochem

journal_title

Journal of cellular biochemistry

authors

Yang F,Li T,Dong Z,Mi R

doi

10.1002/jcb.26405

subject

Has Abstract

pub_date

2018-02-01 00:00:00

pages

2427-2439

issue

eissn

0730-2312

issn

1097-4644

journal_volume

119

pub_type

杂志文章

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MicroRNA-410 is involved in mitophagy after cardiac ischemia/reperfusion injury by targeting high-mobility group box 1 protein.