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PTEN-mediated mitophagy and APE1 overexpression protects against cardiac hypoxia/reoxygenation injury

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Abstract

Autophagy plays a critical role in cardiac hypoxia/reoxygenation (H/R). Studies indicated that the phosphatase and tensin homolog (PTEN) influences level of autophagy. This study aims to explore the role of PTEN mediating a specific autophagy, mitophagy, in cardiac H/R injury. H9c2 cells were cultured and suffered hypoxia and reoxygenation treatment. To inhibit function of PTEN protein, bpv (phen) was added into medium throughout the process of H/R injury. In addition, we overexpressed the apurinic/apyrimidinic endonuclease 1 (APE1) in H/R-injured H9c2 cells. Then the cell viability, apoptosis, and release of Cytochrome C were determined through CCK-8 assay, flow cytometry, and western blotting, respectively. The results indicated that H/R significantly induced autophagy, as identified by an increased level of microtubule-associated protein 1 light chain 3 beta (LC3B) and a decreased level of sequestosome 1 (P62). After stimulation of bpv (phen), PTEN-induced putative kinase protein 1 (PINK1)/Parkin-mediated mitophagy was inhibited, while apoptosis and releases of Cytochrome C were both significantly increased, indicating an exacerbated H/R injury. Furthermore, the overexpression of APE1 attenuated the apoptosis and releases of Cytochrome C induced by H/R injury, and promoted PINK1/Parkin-mediated mitophagy. Our findings provide an insight into the PTEN and APE1 overexpression protects against cardiac hypoxia/reoxygenation injury, which may be through inducing the PINK1/Parkin-mediated mitophagy.

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Authors and Affiliations

  1. Department of Heart and Vascular Surgery, Cardiovascular Disease Center, The Third Affiliated Hospital of Chongqing Medical University, No. 1, Shuang Hu Branch Road, Hui Xing street, Yubei District, Chongqing, 401120, China

    Wenshuai Tang, Deqing Lin, Mingxiang Chen, Zhiping Li, Weimin Zhang, Wenping Hu & Fuping Li

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  1. Wenshuai Tang
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  2. Deqing Lin
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  3. Mingxiang Chen
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  4. Zhiping Li
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  6. Wenping Hu
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  7. Fuping Li
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Correspondence to Fuping Li.

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Editor: Tetsuji Okamoto

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Tang, W., Lin, D., Chen, M. et al. PTEN-mediated mitophagy and APE1 overexpression protects against cardiac hypoxia/reoxygenation injury. In Vitro Cell.Dev.Biol.-Animal 55, 741–748 (2019). https://doi.org/10.1007/s11626-019-00389-6

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