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.

中文翻译：

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PTEN介导的线粒体吞噬和APE1过表达可防止心脏缺氧/复氧损伤。

自噬在心脏缺氧/复氧（H / R）中起关键作用。研究表明，磷酸酶和张力蛋白同源物（PTEN）影响自噬水平。这项研究旨在探讨PTEN在心脏H / R损伤中介导特定的自噬，线粒体吞噬的作用。培养H9c2细胞，并进行缺氧和复氧处理。为了抑制PTEN蛋白的功能，在整个H / R损伤过程中，将bpv（phen）添加到培养基中。此外，我们在H / R损伤的H9c2细胞中过表达了嘌呤/嘧啶内切核酸酶1（APE1）。然后分别通过CCK-8测定，流式细胞术和western印迹法测定细胞活力，细胞凋亡和细胞色素C的释放。结果表明，H / R显着诱导自噬，如微管相关蛋白1轻链3 beta（LC3B）水平升高和螯合物1（P62）水平降低所确定。刺激bpv（phen）后，PTEN诱导的假定激酶蛋白1（PINK1）/ Parkin介导的线粒体被抑制，而细胞凋亡和细胞色素C的释放均显着增加，表明H / R损伤加剧。此外，APE1的过表达减弱了H / R损伤诱导的细胞色素C的凋亡和释放，并促进了PINK1 / Parkin介导的细胞吞噬作用。我们的发现提供了对PTEN和APE1过表达保护免于心脏缺氧/复氧损伤的见解，这可能是通过诱导PINK1 / Parkin介导的细胞吞噬作用。PTEN诱导的假定激酶蛋白1（PINK1）/ Parkin介导的线粒体被抑制，而细胞凋亡和细胞色素C的释放均显着增加，表明H / R损伤加剧。此外，APE1的过表达减弱了H / R损伤诱导的细胞色素C的凋亡和释放，并促进了PINK1 / Parkin介导的细胞吞噬作用。我们的发现提供了对PTEN和APE1过表达保护免于心脏缺氧/复氧损伤的见解，这可能是通过诱导PINK1 / Parkin介导的细胞吞噬作用。PTEN诱导的假定激酶蛋白1（PINK1）/ Parkin介导的线粒体被抑制，而细胞凋亡和细胞色素C的释放均显着增加，表明H / R损伤加剧。此外，APE1的过表达减弱了H / R损伤诱导的细胞色素C的凋亡和释放，并促进了PINK1 / Parkin介导的细胞吞噬作用。我们的发现提供了对PTEN和APE1过表达保护免于心脏缺氧/复氧损伤的见解，这可能是通过诱导PINK1 / Parkin介导的细胞吞噬作用。APE1的过表达减弱了H / R损伤诱导的细胞色素C的凋亡和释放，并促进了PINK1 / Parkin介导的吞噬作用。我们的发现提供了对PTEN和APE1过表达保护免于心脏缺氧/复氧损伤的见解，这可能是通过诱导PINK1 / Parkin介导的细胞吞噬作用。APE1的过表达减弱了H / R损伤诱导的细胞色素C的凋亡和释放，并促进了PINK1 / Parkin介导的吞噬作用。我们的发现提供了对PTEN和APE1过表达保护免于心脏缺氧/复氧损伤的见解，这可能是通过诱导PINK1 / Parkin介导的细胞吞噬作用。