Plasma disturbance of phospholipid metabolism in major depressive disorder by integration of proteomics and metabolomics.

Plasma disturbance of phospholipid metabolism in major depressive disorder by integration of proteomics and metabolomics.
复制标题

通过整合蛋白质组学和代谢组学,磷脂代谢对主要抑郁症的血浆紊乱。

DOI:
10.2147/ndt.s164134
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发表时间:
2018
影响因子:
3.2
通讯作者:
Xie P
Xie P
中科院分区:
医学4区
文献类型:
--
作者:
Gui SW;Liu YY;Zhong XG;Liu X;Zheng P;Pu JC;Zhou J;Chen JJ;Zhao LB;Liu LX;Xu G;Xie P

文献摘要

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重度抑郁症(MDD)是一种非常普遍的精神障碍,影响着全世界数百万人。然而,MDD 的明确病因仍不清楚。在这项研究中,我们的目的是识别 MDD 患者血浆中的关键蛋白质变化,并整合我们的蛋白质组学和之前的代谢组学数据,以揭示 MDD 中显着扰动的途径。采用基于同量异位标签的相对和绝对定量(iTRAQ)的定量蛋白质组学方法来比较抑郁症患者和健康对照(CON)之间的血浆蛋白表达。对于综合分析,Ingenuity Pathway Analysis 软件用于分析蛋白质组学和代谢组学数据,并确定差异蛋白质和代谢物之间的潜在关系。与健康人相比,抑郁症患者共有 74 种蛋白质发生显着变化。差异蛋白的生物信息学分析揭示了脂质转运和代谢功能的显着变化,包括载脂蛋白(APOE、APOC4 和 APOA5)和丝氨酸蛋白酶抑制剂。根据经典通路分析,统计上最显着的前五个通路与脂质转运、炎症和免疫有关。通过整合差异蛋白和代谢物进行因果网络分析表明,磷脂代谢的紊乱可能促进中枢神经系统的炎症。
Major depressive disorder (MDD) is a highly prevalent mental disorder affecting millions of people worldwide. However, a clear causative etiology of MDD remains unknown. In this study, we aimed to identify critical protein alterations in plasma from patients with MDD and integrate our proteomics and previous metabolomics data to reveal significantly perturbed pathways in MDD. An isobaric tag for relative and absolute quantification (iTRAQ)-based quantitative proteomics approach was conducted to compare plasma protein expression between patients with depression and healthy controls (CON). For integrative analysis, Ingenuity Pathway Analysis software was used to analyze proteomics and metabolomics data and identify potential relationships among the differential proteins and metabolites. A total of 74 proteins were significantly changed in patients with depression compared with those in healthy CON. Bioinformatics analysis of differential proteins revealed significant alterations in lipid transport and metabolic function, including apolipoproteins (APOE, APOC4 and APOA5), and the serine protease inhibitor. According to canonical pathway analysis, the top five statistically significant pathways were related to lipid transport, inflammation and immunity. Causal network analysis by integrating differential proteins and metabolites suggested that the disturbance of phospholipid metabolism might promote the inflammation in the central nervous system.