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Berberine Ameliorates Oxygen-glucose Deprivation/Reperfusion-induced Apoptosis by Inhibiting Endoplasmic Reticulum Stress and Autophagy in PC12 Cells

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Summary

This study aimed to elucidate the molecular mechanisms by which berberine protects against cerebral ischemia/reperfusion (I/R) injury. The oxygen-glucose deprivation/reperfusion (OGD/R) PC12 model was established. Cell counting kit-8 (CCK-8) was used to detect the toxicity of berberine and the viability of PC12 cells. Hoechst 33258 staining and flow cytometry were used to observe the nuclear morphology, and changes of apoptosis and reactive oxygen species (ROS), respectively. Western blotting and immunofluorescence assay were employed to detect autophagy-related proteins [microtubule-associated protein 1A/1B-light chain 3 (LC3), P62/SQSTM-1, Beclin-1] and endoplasmic reticulum (ER) stress-related markers [glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), Bcl-2-associated X (Bax) and cleaved caspase-3]. The GFP-RFP-LC3 adenovirus was used to assay the change of autophagic flux. Our results showed that berberine could increase the viability of PC12 cells, decrease the concentrations of ROS after OGD/R treatment, and suppress OGD/R-induced ER stress and autophagy. Moreover, the results revealed the involvement of the mammalian target of rapamycin (mTOR) pathway in the induction of autophagy, and berberine could activate the phosphorylation of mTOR and thus mitigate autophagy. In conclusion, our study suggested that berberine may protect against OGD/R-induced apoptosis by regulating ER stress and autophagy, and it holds promises in the treatment of cerebral I/R injury.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Guizhou Medical University, Guiyang, 550025, China

    Peng Xie, Zhen-kui Ren, Ju Lv, Yu-mei Hu & Wen-feng Yu

  2. Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, Guiyang, 550004, China

    Peng Xie, Zhen-kui Ren, Ju Lv, Yu-mei Hu, Zhi-zhong Guan & Wen-feng Yu

  3. Department of Laboratory Medicine, the Second People’s Hospital of Guizhou Province, Guiyang, 550002, China

    Zhen-kui Ren

  4. Department of Pathology, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China

    Zhi-zhong Guan

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  1. Peng Xie
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  2. Zhen-kui Ren
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  3. Ju Lv
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Correspondence to Wen-feng Yu.

Additional information

This work was supported by grants from the National Natural Science Foundation of China (No. 81360199), Science and Technology Department of Guizhou Province (Guizhou Specific Grant [2019] 4008), Science and Technology Plan Project of Guizhou Province (Basic Science and Technology Cooperation [2020]1Z060), Science and Technology Fund Project of Guizhou Health and Health Commission (No. gzwjkj2019-1-039), and Science and Technology Fund Project of Southwest Guizhou Autonomous Prefecture (2019-1-10).

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All authors confirm that they have no conflicts of interest related to the preset study.

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Xie, P., Ren, Zk., Lv, J. et al. Berberine Ameliorates Oxygen-glucose Deprivation/Reperfusion-induced Apoptosis by Inhibiting Endoplasmic Reticulum Stress and Autophagy in PC12 Cells. CURR MED SCI 40, 1047–1056 (2020). https://doi.org/10.1007/s11596-020-2286-x

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  • DOI: https://doi.org/10.1007/s11596-020-2286-x

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