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β-基酸盐通过对STAT1蛋白的β-基基化抑制M1巨细胞极化

Ya-Ping Bai^1,2, Yu-Jie Xing¹, Tao Ma¹

¹Anhui Provincial Key Laboratory of Non-coding RNA Basic and Clinical Transformation, Wannan Medical College, Wuhu, China.

Cell death & disease

|December 3, 2024

概括

β-甲酸 (β-OHB) 通过氨酸β-甲酸 (Kbhb) 减少炎症性M1巨分化. 这种翻译后的修改影响了关键的炎症信号通路,揭示了新的抗炎机制.

科学领域:

免疫学免疫学免疫学
代谢过程中的代谢.
生物化学生物化学

背景情况:

β-基酸盐 (β-OHB) 是一种具有已知的抗炎性质的体.
通过β-OHB发挥抗炎作用的分子机制,特别是在巨细胞中,尚未完全理解.
lysine β-hydroxybutyrylation (Kbhb) 是一种由β-OHB介导的翻译后修饰,但其在巨细胞功能中的作用在很大程度上尚未被探索.

研究的目的:

为了调查巨细胞是否接受蛋白质Kbhb.
为了确定Kbhb修饰是否调节巨细胞极化.
阐明β-OHB在巨细胞中的抗炎作用的分子机制.

主要方法:

用β-OHB和乙醇治疗小鼠骨髓衍生的巨细胞 (BMDMs),RAW264.7细胞和腹巨细胞 (PMs).
在体外和体内对M1巨细胞极化标记物的评估.
全蛋白质组分析以确定Kbhb修改位点.
西方涂抹和转录分析来检查蛋白质酸化和基因表达.

主要成果:

β-OHB治疗显著降低了脂聚糖 (LPS) 诱导的M1巨细胞两极分化.
在巨细胞中,β-OHB诱导全球蛋白Kbhb,在1549种蛋白中确定了3469个修饰位.
在K679部位的STAT1的Kbhb修饰被确定为一个关键机制,抑制LPS诱导的STAT1酸化和下游转录.
在接受β-OHB治疗的巨细胞中,对介质素-12反应的蛋白质显著上调.

结论:

巨体在对β-OHB的反应中表现出广泛的Kbhb景观.
Kbhb是一种新型的翻译后修饰,可以调节M1巨细胞的两极分化.
β-OHB的抗炎作用部分通过Kbhb诱导的STAT1激活的抑制.
这项研究为β-OHB的抗炎作用及其对巨细胞功能的影响提供了新的见解.

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