Apigenin attenuates myocardial infarction-induced cardiomyocyte injury by modulating Parkin-mediated mitochondrial autophagy

Journal of Biosciences volume 45, Article number: 75 (2020) Cite this article

Abstract

We aimed to detect whether the effect of apigenin (Apig) on the myocardial infarction-induced cardiomyocyte injury of mouse myocardial cells and acute myocardial infarction (AMI) mice was through regulating Parkin expression via miR-103-1-5p. The myocardial infarction cardiomyocyte model (Hypoxia/reoxygenation) was first constructed, then the mouse myocardial cells were treated with Apig, and the expression of miR-103-1-5p was decreased and the expression of Parkin was increased by qRT-PCR and Western blot. It was confirmed by miRNA pulldown and luciferase reporter system that miR-103-1-5p in mouse myocardial cells can bind to Parkin mRNA and inhibit Parkin expression. Next, a lentiviral vector silenced Parkin and overexpressing miR-103-1-5p was constructed and transfected into Apig-treated cells. Autophagy was detected by mitochondrial autophagy marker proteins [atypical protein kinase C (aPKC)-interacting protein (p62) and bcl-2/Adenovirus E1B 19-kd interacting protein 3 (BNIP3)] via Western blot, mitochondrial function was detected by JC-1 probe, and apoptosis was detected by flow cytometry. It was confirmed that Apig regulated mitochondria autophagy through miR-103-1-5p and Parkin, which ultimately affected cardiomyocyte death. Finally, an AMI mouse model was constructed, and then the mice were treated with Apig. The infarct size was detected by triphenyl tetrazolium chloride (TTC) staining, and the Apig relieved the myocardial infarction. The expression of miR-103-1-5p was decreased and the expression of Parkin was increased by qRT-PCR and Western blot. The above results simplified that the cardio protection of Apig and miR-103-1-5p against injury of myocardial infarction cardiomyocyte by targeting Parkin. These results provided a novel treatment against myocardial infarction cardiomyocyte.

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Abbreviations

3′-UTR:

3′ non-coding region

AMI:

acute myocardial infarction

Apig:

apigenin

aPKC:

atypical protein kinase C

BNIP3:

bcl-2/Adenovirus E1B 19-kd interacting protein 3

FCM:

flow cytometry assay

miRNA:

microRNA

MMP:

mitochondrial membrane potential

MUT:

mutant

SD:

standard deviation

TTC:

triphenyl tetrazolium chloride

WT:

wild-type

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Affiliations

  1. State Key Laboratory of Organ Failure Research, Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Ziliang Wang, Hao Zhang, Zuheng Liu, Zhuang Ma, Dongqi An & Dingli Xu

  2. Department of Cardiology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China

    Ziliang Wang

  3. Key Laboratory for Organ Failure Research, Ministry of Education of the People’s Republic of China, Guangzhou, 510515, China

    Ziliang Wang, Hao Zhang, Zuheng Liu, Zhuang Ma, Dongqi An & Dingli Xu

Authors
  1. Ziliang Wang
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  2. Hao Zhang
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  3. Zuheng Liu
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  4. Zhuang Ma
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  5. Dongqi An
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  6. Dingli Xu
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Correspondence to Dingli Xu.

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Corresponding editor: BJ Rao

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Wang, Z., Zhang, H., Liu, Z. et al. Apigenin attenuates myocardial infarction-induced cardiomyocyte injury by modulating Parkin-mediated mitochondrial autophagy. J Biosci 45, 75 (2020). https://doi.org/10.1007/s12038-020-00047-0

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Keywords

  • Apigenin
  • cardiomyocyte injury
  • microRNA-103-1-5p
  • mitochondrial autophagy
  • myocardial infarction
  • Parkin