乳糖氨酸促进了巨细胞的炎症信号传递
bioRxiv : the preprint server for biology
|October 24, 2023
概括
乳酸 (LGSH),而不是乳酸,通过修改组织蛋白驱动炎症. 它的积累,特别是当氧酶2 (GLO2) 缺失时,会增强炎症反应并改变染色体的可访问性.
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,增加糖解和乳酸生产.
- 炎症信号提高了基因激素乳基化,这种改变会影响基因表达.
- 乳糖氨酸 (LGSH) 是参与乳酸化过程的glyoxalase循环中的中间体.
研究的目的:
- 研究LGSH在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,是炎症的关键媒介.
- 探索LGSH在炎症期间对染色质结构的影响.
主要方法:
- 使用的RAW264.7巨细胞缺少糖酶2 (GLO2).
- 暴露细胞的脂多糖 (LPS) 诱导炎症.
- 分析了基因素乳基化水平,染色质可访问性和代谢物生成 (乳基-CoA).
主要成果:
- 缺少GLO2导致LGSH水平升高,并强化LPS诱导的炎症反应.
- 在LPS刺激后,基斯乳基化增加,与增强的炎症相关.
- 乳基化与未受刺激的细胞中紧的染色质有关,在刺激时变得更容易获得.
- 通过自发的LGSH到CoA乙烯转移确定了乳酸CoA生成的新机制.
结论:
- LGSH,而不是细胞内乳酸,是炎症反应的主要驱动因素.
- LGSH积累和随后的基因组乳酸化调节炎症基因表达和染色质动态.
- 甘氨酸酶途径在通过LGSH调节炎症方面发挥着关键作用.
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