由肠道微生物产生的甲氨酸是β2-上腺素受体的内源性全调节剂
Prasenjit Prasad Saha1,2, Valentin Gogonea1,2,3, Wendy Sweet1
1Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH, USA.
肠道细菌代谢物phenylacetylglutamine (PAGln) 作为宿主的负基调制剂 (NAM) 起作用.
科学领域:
- 心血管科学 心血管科学
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 来自肠道微生物群的代谢物在宿主生理学中起作用.
- 乙谷氨 (PAGln) 与心血管疾病 (CVD) 和心力衰竭 (HF) 有关.
- 体调节是代谢调节的关键,但对于肠道微生物群与宿主相互作用没有先前描述过.
研究的目的:
- 为了研究甲基氨酸 (PAGln) 和上腺素受体之间的相互作用.
- 为了确定PAGln是否作为β1-上腺体受体 (β1AR) 或β2-上腺体受体 (β2AR) 的全调节剂.
- 阐明机制,并确定PAGln与β2AR相互作用的特定部位.
主要方法:
- 使用表达β1AR和β2AR的细胞进行基于细胞的测试.
- 在孤立的雄性小鼠心肌细胞和人类失败的心肌的功能研究.
- 在式对接,位点定向的突变发生和功能分析.
主要成果:
- PAGln作为β2AR的负基调制剂 (NAM) 起作用,但不是β1AR.
- 在小鼠心肌细胞和人类心肌中,PAGln表现出NAM效应.
- 在β2AR上发现了特定的残留物 (E122和V206),这些残留物对PAGln的NAM活性至关重要.
结论:
- 肠道微生物群代谢物PAGln是一种宿主β2-上腺素受体 (β2AR) 的内源性负基调制剂 (NAM).
- 这一发现揭示了一个新的肠道微生物群与宿主相互作用机制,涉及GPCRs.
- PAGln对β2AR的调节为心血管疾病提供了潜在的治疗见解.
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