Integrative Proteomics–Metabolomics Strategy for Pathological Mechanism of Vascular Depression Mouse Model,Journal of Proteome Research

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Integrative Proteomics–Metabolomics Strategy for Pathological Mechanism of Vascular Depression Mouse Model
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2017-12-13 00:00:00 , DOI: 10.1021/acs.jproteome.7b00724
Hongxia Zhao ₁ , Hongli Du ₂ , Min Liu ₃ , Songyan Gao ₁ , Na Li ₁ , Yufan Chao ₁ , Ruiqing Li ₄ , Wei Chen ₅ , Ziyang Lou ₁ , Xin Dong ₁

Affiliation

Vascular depression (VD), a subtype of depression, is caused by vascular diseases or cerebrovascular risk factors. Recently, the proportion of VD patients has increased significantly, which severely affects their quality of life. However, the current pathogenesis of VD has not yet been fully understood, and the basic research is not adequate. In this study, on the basis of the combination of LC–MS-based proteomics and metabolomics, we aimed to establish a protein metabolism regulatory network in a murine VD model to elucidate a more comprehensive impact of VD on organisms. We detected 44 metabolites and 304 proteins with different levels in the hippocampus samples from VD mice using a combination of metabolomic and proteomics analyses with an isobaric tags for relative and absolute quantification (iTRAQ) method. We constructed a protein-to-metabolic regulatory network by correlating and integrating the differential metabolites and proteins using ingenuity pathway analysis. Then we quantitatively validated the levels of the bimolecules shown in the bioinformatics analysis using LC–MS/MS and Western blotting. Validation results suggested changes in the regulation of neuroplasticity, transport of neurotransmitters, neuronal cell proliferation and apoptosis, and disorders of amino acids, lipids and energy metabolism. These proteins and metabolites involved in these dis-regulated pathways will provide a more targeted and credible direction to study the mechanism of VD. Therefore, this paper presents an approach and strategy that was applied in integrative proteomics and metabolomics for research and screening potential targets and biomarkers of VD, which could be more precise and credible in a field lacking adequate basic research.

中文翻译：

蛋白质组学—代谢组学策略，用于血管性抑郁症小鼠模型的病理机制

血管性抑郁症（VD）是抑郁症的一种类型，由血管疾病或脑血管危险因素引起。最近，VD患者的比例显着增加，这严重影响了他们的生活质量。但是，目前尚不完全了解VD的发病机理，基础研究还不够充分。在这项研究中，基于LC-MS的蛋白质组学和代谢组学的结合，我们旨在在鼠VD模型中建立蛋白质代谢调控网络，以阐明VD对生物体的更全面影响。我们使用代谢组学和蛋白质组学分析以及同量异位标签对相对和绝对定量（iTRAQ）方法进行了组合，从VD小鼠中检测了44种代谢物和304种蛋白质，并从VD小鼠的海马中检测出不同水平的蛋白质。我们通过使用独创性途径分析来关联和整合差异代谢物和蛋白质，从而构建了蛋白质至代谢的调节网络。然后，我们使用LC-MS / MS和Western blot定量验证了生物信息学分析中显示的双分子水平。验证结果表明神经可塑性调节，神经递质转运，神经元细胞增殖和凋亡以及氨基酸，脂质和能量代谢紊乱的改变。这些参与这些失调途径的蛋白质和代谢产物将为研究VD的机制提供更有针对性和更可靠的方向。因此，本文提出了一种用于蛋白质组学和代谢组学研究和筛选VD潜在靶标和生物标志物的方法和策略，

更新日期：2017-12-13

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