Molecular and Cellular Glycobiology Unit, Department of Biological Science, Sungkyunkwan University, Seoburo 2066, Jangan-Gu, Suwon, Gyunggi-Do 16419, Korea.
Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Samsung Medical Center, Seoul 06351, Korea.
Int J Mol Sci. 2020 Jul 10;21(14):4892. doi: 10.3390/ijms21144892.
N-glycolylneuraminic acid (NeuGc), a non-human sialic acid derivative synthesized by cytidine-5'-monophospho-N-acetylneuraminic acid hydroxylase (CMAH), plays a crucial role in mediating infections by certain pathogens. Although it has been postulated that NeuGc biosynthesis and CMAH expression are downregulated during microbial infection, the underlying mechanisms remain unclear. The present study showed that exposure to lipopolysaccharide (LPS), a Gram-negative bacterial endotoxin, leads to loss of NeuGc biosynthesis in pig small intestinal I2I-2I cells. This LPS-induced NeuGc loss was accompanied by decreased CMAH transcript levels, especially intestine-specific . Furthermore, LPS suppressed the activity of the Pi promoter responsible for by inhibiting DNA binding of Est1. These findings provide insight into the regulatory mechanisms of Neu5Gc biosynthesis during pathogenic infectious events, which may represent a host defense mechanism that protects the self against pathogenic bacterial infections even in non-sanitary environments.
N-羟乙酰神经氨酸（NeuGc）是一种非人类唾液酸衍生物，由胞苷-5'-单磷酸-N-乙酰神经氨酸羟化酶（CMAH）合成，在介导某些病原体感染中起着至关重要的作用。虽然已经假定 NeuGc 生物合成和 CMAH 表达在微生物感染期间下调，但潜在的机制仍不清楚。本研究表明，暴露于脂多糖（LPS），一种革兰氏阴性细菌内毒素，导致猪小肠 I2I-2I 细胞中 NeuGc 生物合成的丧失。这种 LPS 诱导的 NeuGc 丢失伴随着 CMAH 转录本水平的降低，特别是肠特异性的。此外，LPS 通过抑制 Est1 的 DNA 结合来抑制 Pi 启动子对 的活性，从而抑制了 Pi 启动子对 的活性。这些发现为致病性感染事件期间 Neu5Gc 生物合成的调节机制提供了深入了解，这可能代表了一种宿主防御机制，即使在不卫生的环境中，也能保护自身免受致病性细菌感染。
