Berberine Promotes Cardiac Function by Upregulating PINK1/Parkin-Mediated Mitophagy in Heart Failure
Berberine has been verified to protect cardiac function in patients with heart failure (HF). However, the mechanism(s) involved in berberine-mediated cardioprotective effects has not been clearly elucidated. The aim of this study was to further investigate the mechanism(s) involved in the beneficial...
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| Format: | Article |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2020.565751/full |
| _version_ | 1819227304044265472 |
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| author | Miyesaier Abudureyimu Wenjun Yu Richard Yang Cao Yingmei Zhang Haibo Liu Hongchao Zheng |
| author_facet | Miyesaier Abudureyimu Wenjun Yu Richard Yang Cao Yingmei Zhang Haibo Liu Hongchao Zheng |
| author_sort | Miyesaier Abudureyimu |
| collection | DOAJ |
| description | Berberine has been verified to protect cardiac function in patients with heart failure (HF). However, the mechanism(s) involved in berberine-mediated cardioprotective effects has not been clearly elucidated. The aim of this study was to further investigate the mechanism(s) involved in the beneficial effects of berberine on transverse aortic contraction (TAC)-induced chronic HF. Mice were randomly divided into four groups. Berberine was administered at a dose of 50 mg/kg/day for 4 weeks via oral gavage. Our findings showed that TAC-induced pressure overload (PO) prompted cardiac dysfunction, cardiac hypertrophy, interstitial fibrosis, cardiomyocyte apoptosis and mitochondrial injury, accompanied with suppressed mitophagy, the effects of which were attenuated by berberine. Furthermore, mitophagy regulators PINK1 and mito-Parkin were downregulated in TAC-induced HF, while berberine upregulated PINK1/Parkin-mediated mitophagy. Notably, knockdown of PINK1 by small interfering RNA significantly suppressed Parkin-mediated mitochondrial ubiquitination and nullified the beneficial actions on HF exerted by berberine. Taken together, our results indicated that berberine plays a critical role in attenuating cardiac hypertrophy and preserving cardiac function from PO induced HF. The potential underlying mechanism is the activation of mitochondrial autophagy via PINK1/Parkin/Ubiquitination pathway. |
| first_indexed | 2024-12-23T10:39:15Z |
| format | Article |
| id | doaj.art-c29e43158e9d4447bfc61a8f6034f1fb |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-23T10:39:15Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-c29e43158e9d4447bfc61a8f6034f1fb2022-12-21T17:50:13ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-09-011110.3389/fphys.2020.565751565751Berberine Promotes Cardiac Function by Upregulating PINK1/Parkin-Mediated Mitophagy in Heart FailureMiyesaier Abudureyimu0Wenjun Yu1Richard Yang Cao2Yingmei Zhang3Haibo Liu4Hongchao Zheng5Cardiovascular Department, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, ChinaShanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, ChinaCardiovascular Department, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, ChinaShanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Cardiology, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, ChinaCardiovascular Department, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, ChinaBerberine has been verified to protect cardiac function in patients with heart failure (HF). However, the mechanism(s) involved in berberine-mediated cardioprotective effects has not been clearly elucidated. The aim of this study was to further investigate the mechanism(s) involved in the beneficial effects of berberine on transverse aortic contraction (TAC)-induced chronic HF. Mice were randomly divided into four groups. Berberine was administered at a dose of 50 mg/kg/day for 4 weeks via oral gavage. Our findings showed that TAC-induced pressure overload (PO) prompted cardiac dysfunction, cardiac hypertrophy, interstitial fibrosis, cardiomyocyte apoptosis and mitochondrial injury, accompanied with suppressed mitophagy, the effects of which were attenuated by berberine. Furthermore, mitophagy regulators PINK1 and mito-Parkin were downregulated in TAC-induced HF, while berberine upregulated PINK1/Parkin-mediated mitophagy. Notably, knockdown of PINK1 by small interfering RNA significantly suppressed Parkin-mediated mitochondrial ubiquitination and nullified the beneficial actions on HF exerted by berberine. Taken together, our results indicated that berberine plays a critical role in attenuating cardiac hypertrophy and preserving cardiac function from PO induced HF. The potential underlying mechanism is the activation of mitochondrial autophagy via PINK1/Parkin/Ubiquitination pathway.https://www.frontiersin.org/article/10.3389/fphys.2020.565751/fullPINK1mitophagyberberinecardiac hypertrophyheart failure |
| spellingShingle | Miyesaier Abudureyimu Wenjun Yu Richard Yang Cao Yingmei Zhang Haibo Liu Hongchao Zheng Berberine Promotes Cardiac Function by Upregulating PINK1/Parkin-Mediated Mitophagy in Heart Failure Frontiers in Physiology PINK1 mitophagy berberine cardiac hypertrophy heart failure |
| title | Berberine Promotes Cardiac Function by Upregulating PINK1/Parkin-Mediated Mitophagy in Heart Failure |
| title_full | Berberine Promotes Cardiac Function by Upregulating PINK1/Parkin-Mediated Mitophagy in Heart Failure |
| title_fullStr | Berberine Promotes Cardiac Function by Upregulating PINK1/Parkin-Mediated Mitophagy in Heart Failure |
| title_full_unstemmed | Berberine Promotes Cardiac Function by Upregulating PINK1/Parkin-Mediated Mitophagy in Heart Failure |
| title_short | Berberine Promotes Cardiac Function by Upregulating PINK1/Parkin-Mediated Mitophagy in Heart Failure |
| title_sort | berberine promotes cardiac function by upregulating pink1 parkin mediated mitophagy in heart failure |
| topic | PINK1 mitophagy berberine cardiac hypertrophy heart failure |
| url | https://www.frontiersin.org/article/10.3389/fphys.2020.565751/full |
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