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人和小鼠血清总糖组的定量分析。

Quantitative analysis of total serum glycome in human and mouse.

作者信息

Yoshida Yasunobu, Furukawa Jun-Ichi, Naito Shoichi, Higashino Kenichi, Numata Yoshito, Shinohara Yasuro

机构信息

Shionogi Innovation Center for Drug Discovery, Shionogi & Co., Ltd, Sapporo, Japan.

Laboratory of Medical and Functional Glycomics, Graduate School of Advanced Life Science, Hokkaido University, Sapporo, Japan.

出版信息

Proteomics. 2016 Nov;16(21):2747-2758. doi: 10.1002/pmic.201500550. Epub 2016 Oct 12.

Abstract

Model mice are frequently used in drug discovery research. Knowledge of similarities and differences between the mouse and human glycomes is critical when model mice are used for the discovery of glycan-related biomarkers and targets for therapeutic intervention. Since few comparative glycomic studies between human and mouse have been conducted, we performed a comprehensive comparison of the major classes of glycans in human and mouse sera using mass spectrometric and liquid chromatographic analyses. Up to 131 serum glycans, including N-glycans, free oligosaccharides (fOSs), glycosaminoglycans, O-glycans, and glycosphingolipid (GSL)-glycans, were quantified. In both serum samples, N-glycans were the most abundant in the total serum glycome, while fOSs were the least abundant. As expected, the diversity of sialic acid (i.e. Neu5Ac vs. Neu5Gc) was the major species difference between human and mouse in terms of N- and O-glycosylation, while GSL-glycomic profiles were completely different, even when the sialic acid diversity was taken into consideration. Furthermore, total serum glycomics of STAM mouse were unveiled as an initial step to identify novel biomarkers of liver diseases, with which we could identify several glycans with expression significantly increased or decreased expression.

摘要

模型小鼠常用于药物发现研究。当使用模型小鼠来发现与聚糖相关的生物标志物和治疗干预靶点时,了解小鼠和人类糖组之间的异同至关重要。由于很少有人对人和小鼠进行比较糖组学研究,我们使用质谱和液相色谱分析对人和小鼠血清中主要类型的聚糖进行了全面比较。共定量了多达131种血清聚糖,包括N-聚糖、游离寡糖(fOSs)、糖胺聚糖、O-聚糖和糖鞘脂(GSL)-聚糖。在两个血清样本中,N-聚糖在总血清糖组中含量最高,而fOSs含量最低。正如预期的那样,就N-糖基化和O-糖基化而言,唾液酸的多样性(即Neu5Ac与Neu5Gc)是人和小鼠之间的主要物种差异,而即使考虑到唾液酸的多样性,GSL-糖组图谱也完全不同。此外,作为识别肝脏疾病新生物标志物的第一步,我们揭示了STAM小鼠的总血清糖组学,通过它我们可以鉴定出几种表达显著增加或减少的聚糖。

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