Profiling of IgG N-glycome during mouse aging: Fucosylated diantennary glycans containing one Neu5Gc-linked LacNAc are associated with age
Profiling of IgG N-glycome during mouse aging: Fucosylated diantennary glycans containing one Neu5Gc-linked LacNAc are associated with age
复制标题
小鼠衰老过程中 IgG N-糖组的分析：含有一个 Neu5Gc 连接的 LacNAc 的岩藻糖基化二触角聚糖与年龄相关
DOI：
10.1016/j.jprot.2020.103966
复制
发表时间：
2020-10-30
影响因子：
3.3
通讯作者：
Ren, Shifang
中科院分区：
文献类型：
--
作者：
Han, Jing;Pan, Yiqing;Ren, Shifang
免疫球蛋白G(Ig G)的N-糖基化已被报道在人类衰老和一些与年龄相关的疾病中发生变化。为了进一步了解决定这些变化的分子过程，仍然需要对单个免疫球蛋白N-聚糖随年龄的变化进行详细的检查。小鼠是研究衰老和老年性疾病最常用的模型动物，与人类相比，小鼠具有相对可控的遗传和环境变化的优势。本研究采用超高效液相色谱-荧光检测法，系统地研究了衰老12个时间点(6-80周)C57BL/6小鼠血清中N-糖蛋白的变化。这项研究证明了几个重要的发现。首先，首次鉴定了四个层析Ig G N-葡聚糖峰，包括一个高甘露糖多糖、一个单触角多聚糖和两个果糖基化多聚糖。第二，大多数免疫球蛋白多糖水平在6到12周内发生了显著变化，并呈现出明显的性别差异。有趣的是，12周时雄性和雌性小鼠的所有免疫球蛋白多糖水平都趋于相似。第三，含一个N-羟基神经氨酸(Neu5Gc)连接的N-乙酰乳糖胺(LacNAc)的岩藻糖化二触角多聚糖的水平逐渐下降，并与24-80周龄呈显著负相关(r=-0.716，p<；0.0001)，且不存在性别差异。大多数免疫球蛋白N-糖链在小鼠衰老过程中表现出明显的阶段特异性变化和性别差异，表明了糖链合成的严格调控机制。在24-80周龄期间，含有一个Neu5Gc连接的LacNAc的岩藻糖化二天线多糖的水平与年龄呈显著负相关，表明其作为衰老生物标志物的潜力很大。本研究揭示了C57BL/6小鼠Ig G糖基化随年龄变化的详细特征，为在以C57BL/6小鼠模型为基础的增龄相关研究中研究Ig G糖基化的功能和机制提供了必要的参考数据。
N-glycosylation of immunoglobulin G (IgG) has been reported to change in human aging and in some age-related diseases. To further understand the molecular processes that determine these alterations, a detailed examination of individual IgG N-glycans with aging remains required. Mouse is the most commonly used model animal in studies of aging and age-related diseases, and mice have the advantage of relatively controllable genetic and environment variations compared to human. In this study, we systemically investigated the changes in serum IgG N-glycome in C57BL/6 mice during aging at 12 time points (6-80 weeks) via ultraperformance liquid chro-matography with fluorescence detection. The study demonstrated several important findings. First, four chro-matographic IgG N-glycan peaks were identified for the first time, including a high-mannose glycan, a monoantennary glycan, and two afucosylated glycans. Second, most of the IgG glycan levels changed significantly and presented pronounced gender-related differences from 6 to 12 weeks. Interestingly, all the IgG glycan levels tended to be similar between male and female mice at 12 weeks. Third, the level of fucosylated diantennary glycans containing one N-glycolylneuraminic acid (Neu5Gc)-linked N-acetyllactosamine (LacNAc) decreased gradually and showed a significant negative correlation with age from 24 to 80 weeks (r = -0.716, p < 0.0001), which was not sex-specific.Significance: More comprehensive profile of murine IgG N-glycans by ultraperformance liquid chromatography with fluorescence detection was shown in this study with four newly identified chromatographic murine IgG Nglycan peaks. The majority of IgG N-glycans showed substantial stage-specific changes and sex-related differences during mouse aging, indicating a strict regulatory mechanism of glycan synthesis. The level of fucosylated diantennary glycans containing one Neu5Gc-linked LacNAc was significantly negatively correlated with age from 24 to 80 weeks, suggesting its great potential as an aging biomarker. The detailed characteristics of IgG Nglycosylation with aging in C57BL/6 mice demonstrated in the present study could provide essential reference data for studying the function and mechanism of IgG glycosylation in age-related researches based on C57BL/6 mouse models.