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基于深度定量血清糖基化蛋白质组分析的年龄相关早期糖基化蛋白的发现。

Discovery of age-related early-stage glycated proteins based on deep quantitative serum glycated proteome analysis.

机构信息

Shanghai Medical College, Fudan University, Shanghai 200032, China.

Institutes of Biomedical Sciences and Department of Chemistry and NHC Key Laboratory of Glycoconjugates Research, Fudan University, Shanghai 200032, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2023 Oct 25;55(10):1659-1667. doi: 10.3724/abbs.2023222.

DOI:10.3724/abbs.2023222
PMID:37654074
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10577472/
Abstract

Aging is a pressing global health issue that is linked to various diseases, such as diabetes and Alzheimer's disease. It is well known that glycation plays a pathological role in the aging process and age-related diseases. Thus, it is of great significance to discover protein glycation at an early stage for monitoring and intervention in the aging process. However, the endogenous age-related early-stage glycated proteome remains insufficiently profiled. To address this research gap, our study focuses on assessing glycated proteomics profiles in the serum of mice. We employ a robust and quantitative strategy previously developed by our team, to analyze endogenous glycated proteome in serum samples of 4 age groups of mice (10 weeks, 16 weeks, 48 weeks and 80 weeks). In total, 2959 endogenous glycated peptides corresponding to 296 serum proteins are identified from 48 runs of serum samples from 16 mice across the four age groups. By comparing these glycated peptides between adjacent age groups, we discover 49 glycated peptides from 35 proteins that show significant upregulation between the 48-week and 80-week age groups. Furthermore, we identify 10 glycated proteins (or protein groups) that are significantly upregulated only between the 48-week and 80-week age groups, including lecithin-cholesterol acyltransferase (LCAT) and apolipoprotein A-II (Apo A-II). These novel findings provide unique signatures for understanding the aging process and age-related diseases. By shedding light on the early-stage glycated proteome, our study contributes valuable insights that may have implications for future interventions and therapeutic approaches.

摘要

衰老是一个紧迫的全球健康问题,与糖尿病和阿尔茨海默病等多种疾病有关。众所周知,糖基化在衰老过程和与年龄相关的疾病中起着病理性作用。因此,早期发现蛋白质糖基化对于监测和干预衰老过程具有重要意义。然而,内源性与年龄相关的早期糖基化蛋白质组尚未得到充分描述。为了解决这一研究差距,我们的研究重点是评估小鼠血清中的糖基化蛋白质组学图谱。我们采用了我们团队之前开发的一种强大和定量的策略,来分析来自 4 个年龄组(10 周、16 周、48 周和 80 周)的小鼠血清样本中的内源性糖基化蛋白质组。总共从 16 只小鼠的 48 个血清样本运行中鉴定出 2959 个内源性糖基化肽,对应 296 种血清蛋白。通过比较相邻年龄组之间的这些糖基化肽,我们在 48 周和 80 周年龄组之间发现了 35 种蛋白质中的 49 种糖基化肽呈显著上调。此外,我们还鉴定出 10 种糖基化蛋白质(或蛋白质组)仅在 48 周和 80 周年龄组之间显著上调,包括卵磷脂-胆固醇酰基转移酶(LCAT)和载脂蛋白 A-II(Apo A-II)。这些新发现为理解衰老过程和与年龄相关的疾病提供了独特的特征。通过揭示早期糖基化蛋白质组,我们的研究提供了有价值的见解,可能对未来的干预和治疗方法具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd8/10577472/fbd4f1782c8e/ABBS-2023-353-t7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd8/10577472/323f0c536132/ABBS-2023-353-t1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd8/10577472/688380e8436c/ABBS-2023-353-t2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd8/10577472/35e39cd625a8/ABBS-2023-353-t3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd8/10577472/7818ff26da1f/ABBS-2023-353-t4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd8/10577472/9a950a70b871/ABBS-2023-353-t5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd8/10577472/2cca3725a4d9/ABBS-2023-353-t6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd8/10577472/fbd4f1782c8e/ABBS-2023-353-t7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd8/10577472/323f0c536132/ABBS-2023-353-t1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd8/10577472/688380e8436c/ABBS-2023-353-t2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd8/10577472/35e39cd625a8/ABBS-2023-353-t3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd8/10577472/7818ff26da1f/ABBS-2023-353-t4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd8/10577472/9a950a70b871/ABBS-2023-353-t5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd8/10577472/2cca3725a4d9/ABBS-2023-353-t6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/efd8/10577472/fbd4f1782c8e/ABBS-2023-353-t7.jpg

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