Proteomics Profiling with SWATH-MS Quantitative Analysis of Changes in the Human Brain with HIV Infection Reveals a Differential Impact on the Frontal and Temporal Lobes.
Proteomics Profiling with SWATH-MS Quantitative Analysis of Changes in the Human Brain with HIV Infection Reveals a Differential Impact on the Frontal and Temporal Lobes.
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DOI：
10.3390/brainsci11111438
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发表时间：
2021-10-28
期刊：
影响因子：
3.3
通讯作者：
Samikkannu T
中科院分区：
文献类型：
--
作者：
Doke M;Ramasamy T;Sundar V;McLaughlin JP;Samikkannu T
人类免疫缺陷病毒（HIV）相关性痴呆（HAND）中认知能力和记忆功能的慢性不可逆退化与大脑中的晚期HIV感染有关。神经炎症和神经变性的分子水平特征与HAND患者的功能障碍有关。蛋白质表达变化和翻译后修饰是痴呆和神经退行性疾病的表观遗传学线索。在这项研究中，进行定量蛋白质组分析，以全面阐明在HIV阳性（HIV+）人脑蛋白质谱的变化。额叶和颞叶正常和HIV+大脑进行无标记液相色谱-串联质谱（LC-MS/MS）分析，使用数据独立的采集方法。全面的蛋白质组学鉴定和定量分析显示，3294总蛋白和251蛋白在HIV+脑中差异表达;具体而言，HIV+额叶和颞叶分别有132和119个差异表达蛋白。蛋白质组学和生物信息学分析显示，蛋白质的变化主要在HIV+额叶区域。GOLPH 3，IMPDH 2，DYNLL 1，RPL 11和GPNMB蛋白的表达在HIV+额叶中与正常大脑相比显著改变。这些蛋白质与代谢途径、神经退行性疾病和痴呆相关。这些蛋白质组水平的变化可能是潜在的生物学标志物和治疗靶点，以减轻痴呆相关症状的个人与手。
The chronic irreversible regression of cognitive ability and memory function in human immunodeficiency virus (HIV)-associated dementia (HAND) is linked with late-stage HIV infection in the brain. The molecular-level signatures of neuroinflammation and neurodegeneration are linked with dysfunction in HAND patients. Protein expression changes and posttranslational modification are epigenetic cues for dementia and neurodegenerative disease. In this study quantitative proteome analysis was performed to comprehensively elucidate changes in protein profiles in HIV-positive (HIV+) human brains. Frontal and temporal lobes of normal and HIV+ brains were subjected to label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis using the data-independent acquisition method. Comprehensive proteomic identification and quantification analysis revealed that 3294 total proteins and 251 proteins were differentially expressed in HIV+ brains; specifically, HIV+ frontal and temporal lobes had 132 and 119 differentially expressed proteins, respectively. Proteomic and bioinformatic analyses revealed protein alterations predominantly in the HIV+ frontal lobe region. The expression of GOLPH3, IMPDH2, DYNLL1, RPL11, and GPNMB proteins was significantly altered in HIV+ frontal lobes compared to that in normal brains. These proteins are associated with metabolic pathways, neurodegenerative disorders, and dementia. These proteomic-level changes may be potential biological markers and therapeutic targets to relieve the dementia-associated symptoms in individuals with HAND.
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通讯作者：
The Gene Ontology Consortium