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人类海马体中蛋白质乳酸化的全局分析

Global Profiling of Protein Lactylation in Human Hippocampi.

作者信息

Shi Chun-Mei, Wang Qiao-Chu, Li Xiao-Lu, Yang Ye-Hong, Tang Xiao-Yue, Wu Yue, Ding Tao, Zhang Xu-Tong, Zhang Zhi-Yi, Han Ron, Kong Jie, Liu Jiang-Feng, Yang Jun-Tao

机构信息

State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.

出版信息

Proteomics Clin Appl. 2025 Mar;19(2):e202400061. doi: 10.1002/prca.202400061. Epub 2024 Nov 28.

DOI:10.1002/prca.202400061
PMID:39610256
Abstract

PURPOSE

The hippocampus has long been associated with cognition and memory function, the implications of lysine lactylation (Kla), a recently identified post-translational modification (PTM), in the role of the hippocampus remain largely unexplored.

EXPERIMENTAL DESIGN

An LC-MS/MS bottom-up proteomics analysis of three human hippocampal tissue samples was applied to profile the lactylation map in human hippocampi under normal physiological conditions.

RESULTS

We identified 2579 quantifiable Class I lactylated sites in 853 proteins, of which contained four types of modification motifs. Cellular localization analysis implies that a majority of lactylated proteins were distributed in the cytoplasm. Functional enrichment analysis showed that lactylated proteins were mainly involved in energy metabolic pathways. In addition, we found that the lactylation on histones exhibits a certain degree of conservation across different tissues. Compared with previously reported lactylation databases, 213 lactylated proteins were identified for the first time in this study.

CONCLUSION AND CLINICAL RELEVANCE

The first global lactylated proteins atlas of human hippocampi was reported in this study. Our work provides a reliable foundation for further research on lactylation in the hippocampus under physiological conditions.

摘要

目的

海马体长期以来一直与认知和记忆功能相关联,赖氨酸乳酰化(Kla)作为一种最近发现的翻译后修饰(PTM),其在海马体中的作用在很大程度上仍未得到探索。

实验设计

应用液相色谱 - 串联质谱(LC-MS/MS)自下而上的蛋白质组学分析方法,对三个人类海马组织样本进行分析,以描绘正常生理条件下人类海马体中的乳酰化图谱。

结果

我们在853种蛋白质中鉴定出2579个可定量的I类乳酰化位点,其中包含四种类型的修饰基序。细胞定位分析表明,大多数乳酰化蛋白质分布在细胞质中。功能富集分析表明,乳酰化蛋白质主要参与能量代谢途径。此外,我们发现组蛋白上的乳酰化在不同组织中表现出一定程度的保守性。与先前报道的乳酰化数据库相比,本研究首次鉴定出213种乳酰化蛋白质。

结论与临床意义

本研究报道了首个全面的人类海马体乳酰化蛋白质图谱。我们的工作为进一步研究生理条件下海马体中的乳酰化提供了可靠的基础。

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