酸侧链O-乙化损失加剧大肠炎
Yang Ji1, Shubham Parashar1, Yukiko Miyamoto1
1Department of Medicine, University of California San Diego, La Jolla, CA 92093.
概括
酶CASD1为酸 (Sias) 添加O-乙基,这对于肠道保护至关重要. 这种修饰的损失会使结肠炎恶化,并影响肠道微生物.
科学领域:
- 生物化学 生物化学
- 葡萄糖生物学 葡萄糖生物学
- 免疫学 免疫学 免疫学
背景情况:
- 酸 (Sias) 是细胞表面的终端甘氨酸,在粘膜部位大量存在.
- 在基基上 (C7-C9) 的Sias的O-乙化,由于可变性,提出了分析挑战.
- 了解O-乙 Sia的修饰对于它们的功能作用至关重要.
研究的目的:
- 分析O-乙 Sia修饰的表达和功能.
- 调查CASD1在Sias的O-乙化中的作用.
- 确定Sia O-乙化对肠道健康和炎症的影响.
主要方法:
- 使用sialoglycan识别探针和HPLC分析DMB衍生Sias.
- 研究的小鼠缺乏酸盐O-乙转移酶,CASD1.
- 在野生型和CASD1缺乏的小鼠中比较O-乙化含量,包括无菌条件.
- 在小鼠中诱导大肠炎,以评估CASD1和Sia O-乙化在炎症中的作用.
主要成果:
- C7/C9-O-乙化Sias在结肠中最为丰富,在其他组织中含量较低.
- CASD1缺陷显著降低了C7/C9-O-乙化Sias,独立于微生物群.
- 缺乏CASD1的小鼠表现出恶化的结肠炎,在结肠炎和IBD患者中观察到减少的Sia O-乙化.
结论:
- CASD1 是主要负责Sias.C7/C8/C9-O-乙化的主要酶.
- O-乙化提供了肠道保护功能,可能通过限制微生物代谢.
- 减少Sia O-乙化与肠道炎症的严重程度增加有关.
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