Beclin‑1 exerts protective effects against cerebral ischemia‑reperfusion injury by promoting DNA damage repair through a non‑autophagy‑dependent regulatory mechanism

Luo,Hongcheng; Huang,Deyou; Tang,Xionglin; Liu,Yu; Luo,Qisheng; Liu,Chunhong; Huang,Huatuo; Chen,Wencheng; Qi,Zhongquan

doi:10.3892/ijmm.2022.5117

Beclin‑1 exerts protective effects against cerebral ischemia‑reperfusion injury by promoting DNA damage repair through a non‑autophagy‑dependent regulatory mechanism

Authors:
- Hongcheng Luo
- Deyou Huang
- Xionglin Tang
- Yu Liu
- Qisheng Luo
- Chunhong Liu
- Huatuo Huang
- Wencheng Chen
- Zhongquan Qi
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Affiliations: Department of Biology, Medical College of Guangxi University, Nanning, Guangxi 530004, P.R. China, Department of Radiology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China, Department of Neurology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China, Department of Biology, Medical College of Guangxi University, Nanning, Guangxi 530004, P.R. China, Department of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China, Department of Laboratory Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China, Department of Laboratory Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China
Published online on: March 10, 2022 https://doi.org/10.3892/ijmm.2022.5117
Article Number: 61
Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cerebral ischemia‑reperfusion (I/R) can result in severe brain injury, for which there are no optimal treatment options. I/R is often accompanied by increased autophagy. Beclin‑1, a central player in autophagy, has been extensively studied in I/R; however, to date, at least to the best of our knowledge, there are no definitive descriptions of its specific role. Thus, the aim of the present study was to explore the regulatory role played by Beclin‑1 in I/R. In vivo experiments were performed using an animal model of brain I/R with male Sprague‑Dawley rats. Brain tissue damage was observed using 2,3,5‑triphenyltetrazolium chloride, and hematoxylin and eosin staining. Tissue apoptosis levels were evaluated using a TUNEL assay, as well as western blot analysis. Immunofluorescence together with western blot analysis was used to detect autophagy in the tissues. Immunohistochemistry and western blot analysis were used to analyze DNA double‑stranded breaks (DSBs). Moreover, HT22 cells overexpressing Beclin‑1 were subjected to oxygen glucose deprivation/reoxygenation injury to simulate I/R pathological damage in vitro. Apoptosis was assessed using TUNEL and flow cytometric assays in this in vitro model, and autophagy was assessed using immunofluorescence and western blot analysis. The DSBs of the cells were analyzed using western blot analysis. I/R activated autophagy and induced DSBs. Autophagy inhibitors decreased brain tissue damage and reduced cell apoptosis; however, the degree of decrease in damage and apoptosis was not highly associated with the change in autophagy, and the frequency of DSBs slightly increased. The overexpression of Beclin‑1 in neurons significantly attenuated I/R‑induced damage and promoted DSB repair. On the whole, the present study demonstrates that Beclin‑1 protects neurons from ischemic damage through the non‑autophagy‑dependent regulation of DNA repair processes.

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