乳甲基促进了巨细胞的炎症信号传递,通过组织素乳基化
Marissa N Trujillo1, Erin Q Jennings1, Emely A Hoffman1
1Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA.
Molecular metabolism
|February 2, 2024
概括
乳酸 (LGSH),而不是乳酸,驱动着基因素乳酸和炎症反应. 氧酶2 (GLO2) 缺乏会增加LGSH,增强炎症并改变炎症信号传递期间的染色质可访问性.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 慢性炎症与代谢障碍有关,其特点是糖解和乳酸生产增加.
- 转录的调节者 - - 希斯乳基化,在炎症期间随着乳酸水平的上升而上升.
- 乳糖氨酸 (LGSH) 是一种糖酶循环中介物,涉及到组织素乳酸化.
研究的目的:
- 调查LGSH在基因素乳基化和炎症信号传递中的调节作用.
- 为了确定LGSH,而不是细胞内乳酸,是基因素乳基化的主要驱动因素.
- 探索LGSH对炎症期间染色质可访问性的影响.
主要方法:
- 使用了RAW264.7巨细胞,包括缺少谷氨酸酶2 (GLO2) 的细胞.
- 用脂多糖 (LPS) 刺激的巨细胞.
- 评估了基因组乳基化,LGSH水平,染色质可访问性和乳基CoA生成.
主要成果:
- GLO2 缺乏导致LGSH和基因素乳基化升高,增强LPS诱导的炎症反应.
- 希斯乳基化与未受刺激细胞中的紧色素有关,但在刺激时可获得性增加.
- 通过自发性转移从LGSH识别出一种新的乳酸甲基CoA生成途径.
结论:
- 而LGSH,而不是细胞内乳酸盐,是基因素乳基化的主要媒介,也是炎症信号的关键贡献者.
- 甘氨酸酶系统在通过基因素乳基化调节炎症反应方面发挥着至关重要的作用.
- LGSH是一个关键的代谢物,将代谢状态与炎症基因表达和染色质动态联系起来.
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