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阿尔茨海默病患者血清、红细胞和脑脊液中的硒水平:来自澳大利亚衰老成像、生物标志物与生活方式旗舰研究(AIBL)的报告

Selenium Levels in Serum, Red Blood Cells, and Cerebrospinal Fluid of Alzheimer's Disease Patients: A Report from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL).

作者信息

Cardoso Bárbara R, Hare Dominic J, Bush Ashley I, Li Qiao-Xin, Fowler Christopher J, Masters Colin L, Martins Ralph N, Ganio Katherine, Lothian Amber, Mukherjee Soumya, Kapp Eugene A, Roberts Blaine R

机构信息

The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.

Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, SP, Brazil.

出版信息

J Alzheimers Dis. 2017;57(1):183-193. doi: 10.3233/JAD-160622.

Abstract

Selenium (Se) protects cells against oxidative stress damage through a range of bioactive selenoproteins. Increased oxidative stress is a prominent feature of Alzheimer's disease (AD), and previous studies have shown that Se deficiency is associated with age-related cognitive decline. In this study, we assessed Se status in different biofluids from a subgroup of participants in the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing. As Se in humans can either be an active component of selenoproteins or inactive via non-specific incorporation into other proteins, we used both size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) and tandem mass spectrometry to characterize selenoproteins in serum. We observed no differences in total Se concentration in serum or cerebrospinal fluid of AD subjects compared to mildly cognitively impairment patients and healthy controls. However, Se levels in erythrocytes were decreased in AD compared to controls. SEC-ICP-MS analysis revealed a dominant Se-containing fraction. This fraction was subjected to standard protein purification and a bottom-up proteomics approach to confirm that the abundant Se in the fraction was due, in part, to selenoprotein P. The lack of change in the Se level is at odds with our previous observations in a Brazilian population deficient in Se, and we attribute this to the Australian cohort being Se-replete.

摘要

硒(Se)通过一系列生物活性硒蛋白保护细胞免受氧化应激损伤。氧化应激增加是阿尔茨海默病(AD)的一个显著特征,先前的研究表明,硒缺乏与年龄相关的认知衰退有关。在本研究中,我们评估了澳大利亚衰老成像、生物标志物和生活方式旗舰研究中一部分参与者不同生物流体中的硒状态。由于人体中的硒既可以是硒蛋白的活性成分,也可以通过非特异性掺入其他蛋白质而处于非活性状态,我们使用尺寸排阻色谱-电感耦合等离子体质谱法(SEC-ICP-MS)和串联质谱法来表征血清中的硒蛋白。与轻度认知障碍患者和健康对照相比,我们观察到AD患者血清或脑脊液中的总硒浓度没有差异。然而,与对照组相比,AD患者红细胞中的硒水平降低。SEC-ICP-MS分析显示出一个主要的含硒组分。对该组分进行标准蛋白质纯化和自下而上的蛋白质组学方法,以确认该组分中丰富的硒部分归因于硒蛋白P。硒水平缺乏变化与我们之前在缺硒的巴西人群中的观察结果不一致,我们将此归因于澳大利亚队列硒充足。

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