Wang Yamei, Zhao Jian, Sun Liang, Xu Dingding, Wei Xiaoming, Li Jia, Mo Zihan, Xia Nian, Zhou Junge, Yao Yuan, Hu Qiao, Zhou Qingqing
Department of Neurology, The First Affiliated Hospital of Yangtze University, Jingzhou First People's Hospital, Jingzhou, 434000, China.
Department of Neurosurgery, The First Affiliated Hospital of Yangtze University, Jingzhou First People's Hospital, Jingzhou, 434000, China.
BMC Neurol. 2025 Apr 10;25(1):153. doi: 10.1186/s12883-025-04171-y.
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.
In this study, PC12 cells (a rat adrenal pheochromocytoma cell line) were exposed to Cobalt chloride (CoCl) 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 CoCl-induced hypoxia damage.
RES attenuated CoCl-induced decreases of cell viability and cell proliferation and increase of ROS production in PC12 cells. CoCl downregulated Kbhb in PC12 cells, but RES alleviated this effect. In addition, upregulated Kbhb by 3-hydroxybutyric acid sodium could partially recover the CoCl-induced hypoxia damage to PC12 cells, including cell viability, cell proliferation, oxidative stress, and the protein level of the inflammatory signaling factor P65.
Our results indicate that RES protects against CoCl-induced hypoxia damage in PC12 cells by modulating Kbhb, a novel post-translational modification.
中风是一种脑血管疾病，是全球范围内死亡和残疾的主要原因。缺氧是导致神经元损伤甚至细胞死亡的主要因素。然而，缺氧的机制和治疗药物尚未完全明确。
在本研究中，将PC12细胞（大鼠肾上腺嗜铬细胞瘤细胞系）暴露于氯化钴（CoCl）以诱导缺氧。利用该细胞模型，研究缺氧对细胞活力、增殖、活性氧（ROS）、赖氨酸β-羟基丁酰化（Kbhb）水平以及炎症信号因子P65的影响。此外，我们探讨了白藜芦醇（RES）减轻CoCl诱导的缺氧损伤的能力。
RES减轻了CoCl诱导的PC12细胞活力和细胞增殖的降低以及ROS产生的增加。CoCl下调了PC12细胞中的Kbhb，但RES减轻了这种作用。此外，用3-羟基丁酸钠上调Kbhb可部分恢复CoCl诱导的PC12细胞缺氧损伤，包括细胞活力、细胞增殖、氧化应激以及炎症信号因子P65的蛋白水平。
我们的结果表明，RES通过调节Kbhb（一种新的翻译后修饰）来保护PC12细胞免受CoCl诱导的缺氧损伤。
