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SARM1调节NAD+相关代谢,并在巨细胞中选择免疫基因

Katharine A Shanahan¹, Gavin M Davis¹, Ciara G Doran¹

¹School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.

The Journal of biological chemistry

|January 4, 2024

概括

无菌的α和HEAT/armadillo图案含有蛋白质 (SARM1) 调节巨细胞代谢和免疫基因表达. 缺少SARM1会改变NAD+水平,促进糖解和氧化酸化,影响炎症反应.

科学领域:

免疫学免疫学免疫学
细胞的新陈代谢
分子生物学分子生物学

背景情况:

无菌α和HEAT/armadillo motif含有蛋白质 (SARM1) 是一种消耗NAD+的酶,参与免疫反应.
神经SARM1通过其NADase活性导致轴突退化.
在巨细胞代谢中SARM1的作用仍然未被探索.

研究的目的:

研究SARM1对巨细胞代谢和免疫基因表达的影响.
确定SARM1缺乏如何影响巨细胞中的NAD+度和细胞呼吸.

主要方法:

在野生型 (WT) 和Sarm1-/-巨细胞中分析NAD+和循环ADP-核糖水平.
氧化酸化和糖解的评估.
在脂多糖 (LPS) 或IL-4刺激后对基因表达 (Interleukin-1beta,Interleukin-10,Fizz1) 的评估.

主要成果:

萨姆1-/-巨体呈现出较高的NAD+和减少的循环ADP-核糖.
SARM1缺乏增加了氧化酸化和糖解的储备能力.
在LPS刺激后,SARM1限制了糖解和促炎基因表达 (Il1b).
在IL-4刺激后,SARM1缺乏增强了糖解和氧化酸化,但降低了抗炎基因表达 (Fizz1).

结论:

在微调巨细胞代谢中,SARM1起着至关重要的作用.
SARM1通过NAD+消耗和代谢变化影响免疫基因转录.
SARM1作为一种代谢性风静止剂,控制巨细胞中的炎症和抗炎反应.

关键词:

这是NAD (((+)纳达酶 NADase 是一个这就是SARM1的作用.cADPR是指一个在线的平台.诱导细胞因子诱导巨细胞是什么?巨细胞是什么?代谢代谢代谢代谢

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