2. Academic Validation
  3. Resveratrol attenuates the CoCl2-induced hypoxia damage by regulation of lysine β-hydroxybutyrylation in PC12 cells

Resveratrol attenuates the CoCl2-induced hypoxia damage by regulation of lysine β-hydroxybutyrylation in PC12 cells

  • BMC Neurol. 2025 Apr 10;25(1):153. doi: 10.1186/s12883-025-04171-y.
Yamei Wang # 1,  Jian Zhao # 2,  Liang Sun # 3,  Dingding Xu 2,  Xiaoming Wei 2,  Jia Li 4,  Zihan Mo 4,  Nian Xia 4,  Junge Zhou 5,  Yuan Yao 6,  Qiao Hu 7,  Qingqing Zhou 8
Affiliations

Affiliations

  • 1 Department of Neurology, The First Affiliated Hospital of Yangtze University, Jingzhou First People's Hospital, Jingzhou, 434000, China.
  • 2 Department of Neurosurgery, The First Affiliated Hospital of Yangtze University, Jingzhou First People's Hospital, Jingzhou, 434000, China.
  • 3 Postgraduate Training Base Alliance of WenZhou Medical University (PTBAWMU), WenZhou, 325035, Zhejiang Province, China.
  • 4 School of clinical medicine, Yangtze University, Jingzhou, 434000, China.
  • 5 Department of Neurosurgery, General Hospital of the Yangtze River Shipping (Wuhan Brain Hospital), Wuhan, 430010, China. 43494830@qq.com.
  • 6 Department of Neurosurgery, The First Affiliated Hospital of Yangtze University, Jingzhou First People's Hospital, Jingzhou, 434000, China. 49246670@qq.com.
  • 7 Department of Neurology, The First Affiliated Hospital of Yangtze University, Jingzhou First People's Hospital, Jingzhou, 434000, China. 173505051@qq.com.
  • 8 Department of Neurosurgery, The First Affiliated Hospital of Yangtze University, Jingzhou First People's Hospital, Jingzhou, 434000, China. 397406589@qq.com.
  • # Contributed equally.
PMID: 40211144 DOI: 10.1186/s12883-025-04171-y
Abstract

Background: Stroke is a cerebrovascular disease that is the main cause of death and disability worldwide. Hypoxia is a major factor that causes neuronal damage and even cellular death. However, the mechanism and therapeutic drugs for hypoxia are not completely understood.

Methods: In this study, PC12 cells (a rat adrenal pheochromocytoma cell line) were exposed to Cobalt chloride (CoCl2) to induce hypoxia. Using this cell model, the impacts of hypoxia on cell viability, proliferation, Reactive Oxygen Species (ROS), and the levels of lysine β-hydroxybutyrylation (Kbhb) and the inflammatory signaling factor P65 were examined. In addition, we explored the ability of resveratrol (RES) to alleviate CoCl2-induced hypoxia damage.

Results: RES attenuated CoCl2-induced decreases of cell viability and cell proliferation and increase of ROS production in PC12 cells. CoCl2 downregulated Kbhb in PC12 cells, but RES alleviated this effect. In addition, upregulated Kbhb by 3-hydroxybutyric acid sodium could partially recover the CoCl2-induced hypoxia damage to PC12 cells, including cell viability, cell proliferation, oxidative stress, and the protein level of the inflammatory signaling factor P65.

Conclusion: Our results indicate that RES protects against CoCl2-induced hypoxia damage in PC12 cells by modulating Kbhb, a novel post-translational modification.

Keywords

CoCl2; Hypoxia; Lysine β-hydroxybutyrylation; PC12 cells; Reactive oxygen species; Resveratrol.

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