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Globular adiponectin protects hepatocytes against intermittent hypoxia-induced injury via Pink1/Parkin-mediated mitophagy induction

  • Basic Science • Original Article
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Abstract

Purpose

This study sought to determine the effect of Pink1/Parkin-mediated mitophagy on liver cells exposed to intermittent hypoxia (IH) and the roles of globular adiponectin (gAPN).

Methods

The hepatocyte model of IH was established. Cell apoptosis was assessed using flow cytometry. Mitochondrial membrane potential (MMP) level was determined using JC-1, and mitophagy was assessed using a confocal laser. Mitochondrial injury associated protein levels of bax and bcl-2, and protein levels of Pink1 and Parkin were evaluated via western blotting. We downregulated Parkin expression by transfecting the cells with Parkin siRNA.

Results

Pink1 and Parkin protein levels, mitophagy, and cell apoptosis rate were high, while the MMP level and protein level ratio of bcl-2/bax were low in IH-treated hepatocyte. gAPN upregulated Pink1 and Parkin protein levels, MMP level, protein level ratio of bcl-2/bax, and mitophagy while it reduced the rate of cell apoptosis in IH-treated hepatocytes. Inhibiting Parkin expression significantly reduced mitophagy and increased mitochondrial injury and the rate of hepatocyte apoptosis under IH or IH with gAPN.

Conclusion

gAPN alleviated IH-induced mitochondrial injury and hepatocyte apoptosis by upregulating Pink1/Parkin-mediated mitophagy.

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Data availability

All data generated or analyzed during this study are included in this published article.

Code availability

Not applicable.

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Funding

This work was supported by the National Natural Science Foundation of China (grant numbers 81770086 and 81700090).

Author information

Authors and Affiliations

  1. Department of Pulmonary and Critical Care Medicine, ZhongDa Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, China

    Wenxiao Ding

  2. Department of Emergency, Nanjing Medical University First Affiliated Hospital, 300 Guangzhou Road, Nanjing, 210029, China

    Yanbin Dong

  3. Department of Pulmonary and Critical Care Medicine, Nanjing Medical University First Affiliated Hospital, 300 Guangzhou Road, Nanjing, 210029, China

    Xilong Zhang

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  1. Wenxiao Ding
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Contributions

Conceptualization, Xilong Zhang, Yanbin Dong, and Wenxiao Ding. Methodology, Xilong Zhang, Yanbin Dong, and Wenxiao Ding. Formal analysis and investigation, Xilong Xhang, Yanbin Dong, and Wenxiao Ding. Writing — original draft preparation, Xilong Zhang, Yanbin Dong, and Wenxiao Ding. Writing — review and editing, Xiong Zhang and Wenxiao Ding. Funding acquisition, Xilong Zhang and Wenxiao Ding. Resources, Xilong Zhang, Yanbin Dong, and Wenxiao Ding. Supervision, Xilong Zhang.

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Correspondence to Xilong Zhang.

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Ding, W., Dong, Y. & Zhang, X. Globular adiponectin protects hepatocytes against intermittent hypoxia-induced injury via Pink1/Parkin-mediated mitophagy induction. Sleep Breath 26, 1389–1397 (2022). https://doi.org/10.1007/s11325-021-02508-8

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  • DOI: https://doi.org/10.1007/s11325-021-02508-8

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