在lps激活的小胶质细胞中通过PKM2去乙酰化调节sirt2介导的糖酵解和炎症。

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-06-06 DOI:10.1016/j.brainres.2025.149763

Qunshan Chen , Weixian Xu , Xiaofang Tong , Mei Cheng

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引用次数: 0

摘要

背景：抑制炎症和小胶质细胞糖酵解有助于神经性疼痛的治疗。从多种植物中分离出来的化合物，具有多种抗炎、抗肿瘤作用。目的：探讨皂苷对小胶质细胞活化的治疗潜力及作用机制。方法：采用LPS处理BV2小胶质细胞模拟体外神经性疼痛微环境，采用qPCR阵列分析Ononin处理后BV2小胶质细胞的基因表达情况。然后研究了Ononin和SIRT2基因对炎症和糖酵解的影响。利用GPS-PAL数据库预测PKM2乙酰化位点。我们还研究了PKM2与SIRT2蛋白之间的相互作用。结果：40 μM的Ononin显著抑制lps处理的BV2小胶质细胞的炎症和糖酵解，这与SIRT2水平上调有关。抑制SIRT2削弱了Ononin的调节作用，诱导PKM2乙酰化，增强BV2细胞的糖酵解。SIRT2对PKM2蛋白的K207位点进行去乙酰化修饰，降低PKM2蛋白的稳定性。结论：SIRT2介导的代谢重编程和炎症对神经性疼痛至关重要，Ononin通过调节SIRT2以去乙酰化方式抑制PKM2蛋白的稳定性，显示出治疗潜力，提示其是一种有前景的治疗选择。

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Ononin modulates SIRT2-mediated glycolysis and inflammation in LPS-activated microglia via PKM2 deacetylation

Background

Inhibition of inflammation and glycolysis of microglia contributes to neuropathic pain treatment. Ononin, a compound isolated from various plants, has been found to have various anti-inflammatory and anti-tumor effects.

Aim

To investigate the therapeutic potential and mechanism of Ononin on microglial activation.

Methods

BV2 microglial cells were treated with LPS to mimic microenvironment of neuropathic pain in vitro, and gene expression was analyzed by qPCR array analysis after Ononin treatment. The effects of Ononin and SIRT2 gene on inflammation and glycolysis were then investigated. PKM2 acetylation sites were predicted using the GPS-PAL database. The interaction between PKM2 and SIRT2 protein was also studied.

Results

Ononin at 40 μM significantly inhibited inflammation and glycolysis in LPS-treated BV2 microglial cells, and this was related to the upregulation of SIRT2 levels. Inhibition of SIRT2 weakened the regulatory effects of Ononin, and induced PKM2 acetylation to enhance glycolysis in BV2 cells. SIRT2 exerts deacetylation modification at K207 site of PKM2 protein to reduce the stability of PKM2 protein.

Conclusions

SIRT2-mediated metabolic reprogramming and inflammation are critical for neuropathic pain, and Ononin shows therapeutic potential by modulating SIRT2 to suppress PKM2 protein stability in the deacetylation way, suggesting it as a promising treatment option.

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.