循环宿主和微生物托芬代谢物对AH受体激活的贡献
Ethan W Morgan1, Fangcong Dong2, Andrew J Annalora3
1Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, USA.
International journal of tryptophan research : IJTR
|July 13, 2023
概括
主体新陈代谢从酸中产生关键的酸受体 (AHR) 激活剂. 这项研究揭示了循环的托芬代谢物,而不仅仅是肠道细菌,对于AHR活动和恒温至关重要.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
背景情况:
- 酸受体 (AHR) 调节关键的细胞功能,包括免疫反应和新陈代谢.
- 来自宿主和肠道微生物代谢的托芬代谢物是已知的AHR激活剂.
- 这些循环中的代谢物的确切来源和作用尚不清楚.
研究的目的:
- 在小鼠和人类中研究循环AHR激活托代谢物的代谢来源.
- 探索这些代谢物的生物相关性,特别是当它们以混合物形式存在时.
- 通过考虑无处不在的托代谢物在恒温和疾病中的作用,重新构建AHR生物学.
主要方法:
- 从常规,无细菌小鼠和人类的血清中基于向质谱的代谢物概况.
- 基于细胞的测试,以评估单个和聚合的托代谢物的AHR激活潜力.
- 带结合竞争测试和对接模拟以确定AHR激动剂.
- 针对类风湿性关节炎的基于细胞模型的研究.
主要成果:
- 许多托芬代谢物的血清度在无菌和常规小鼠中相似,这表明存在显著的宿主生产.
- 主体新陈代谢,而不仅仅是肠道细菌,是循环的AHR激活托代谢物的主要来源.
- 在相关度下使用复杂的代谢物混合物研究了AHR激活.
- 鉴定的代谢物在风湿性关节炎模型中显示出生理和生物医学相关性.
结论:
- 来自宿主的托芬代谢物是循环AHR活动的重要贡献者.
- 了解AHR激活需要考虑生理度的代谢物混合物.
- 这项工作重新定义了AHR生物学,强调了无处不在的代谢物在维持平衡和在诸如类风湿关节炎等AHR相关疾病中的重要性.
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