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Cerebrospinal fluid: Profiling and fragmentation of gangliosides by ion mobility mass spectrometry.
Biochimie ( IF 3.9 ) Pub Date : 2019-12-17 , DOI: 10.1016/j.biochi.2019.12.008
Mirela Sarbu 1 , Shannon Raab 2 , Lucas Henderson 2 , Dragana Fabris 3 , Željka Vukelić 3 , David E Clemmer 2 , Alina D Zamfir 4
Affiliation  

The proximity of cerebrospinal fluid (CSF) with the brain, its permanent renewal and better availability for research than tissue biopsies, as well as ganglioside (GG) shedding from brain to CSF, impelled lately the development of protocols for the characterization of these glycoconjugates and discovery of central nervous system biomarkers expressed in CSF. Currently, the investigation of CSF gangliosides is focused on concentration measurements of the predominant classes and much less on their profiling and structural analysis. Since we have demonstrated recently the high performance of ion mobility separation mass spectrometry (IMS MS) for compositional and structural determination of human brain GGs, in the present study we have implemented for the first time IMS MS for the exploration of human CSF gangliosidome, in order to generate the first robust mass spectral database of CSF gangliosides. IMS MS separation and screening revealed 113 distinct GG species in CSF, having similar compositions to the species detected in human brain. In comparison with the brain tissue, we have discovered in CSF several components containing fatty acids with odd number of carbon atoms and/or short glycan chains. By tandem MS (MS/MS) we have further analyzed the structure of GD3(d18:1/18:0) and GD2(d18:1/18:0), two glycoforms exhibiting short carbohydrate chains found in CSF, but discovered and characterized previously in brain as well. According to the present results, human CSF and brain show a similar ganglioside pattern, a finding that might be useful in clinical research focused on discovery of ganglioside species associated to neurodegenerative diseases and brain tumors.

中文翻译:

脑脊液:通过离子迁移质谱法分析神经节苷脂并使其破碎。

脑脊液(CSF)与大脑的距离近,其永久性更新和比组织活检更适合研究的需要,以及神经节苷脂(GG)从脑部流向CSF的发展,最近促进了表征这些糖结合物和蛋白质的方案的发展。发现在脑脊液中表达的中枢神经系统生物标志物。目前,对脑脊液神经节苷脂的研究集中在主要类别的浓度测量上,而很少涉及它们的概况和结构分析。由于我们最近证明了离子淌度分离质谱(IMS MS)在测定人脑GG的成分和结构方面的高性能,因此在本研究中,我们首次实施了IMS MS来探索人的CSF神经节苷脂,为了产生第一个健壮的脑脊液神经节苷脂质谱数据库。IMS MS分离和筛选揭示了CSF中113种不同的GG种类,其组成与人脑中检测到的种类相似。与脑组织相比,我们在脑脊液中发现了几种成分,这些成分包含具有奇数碳原子和/或短聚糖链的脂肪酸。通过串联质谱(MS / MS),我们进一步分析了GD3(d18:1/18:0)和GD2(d18:1/18:0)的结构,这两种糖型均表现出在CSF中发现的短碳水化合物链,但已发现并以前在大脑中也有特征。根据目前的结果,人类脑脊液和大脑显示出类似的神经节苷脂模式,
更新日期:2019-12-18
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