Cerebrospinal fluid: Profiling and fragmentation of gangliosides by ion mobility mass spectrometry
| Autor: | David E. Clemmer, Dragana Fabris, Alina D. Zamfir, Mirela Sarbu, Željka Vukelić, Lucas W. Henderson, Shannon A. Raab |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Glycan Spectrometry Mass Electrospray Ionization Collision-induced dissociation Glycoconjugate Central nervous system Mass spectrometry Biochemistry 03 medical and health sciences Cerebrospinal fluid Gangliosides medicine Humans chemistry.chemical_classification Brain Diseases Ganglioside 030102 biochemistry & molecular biology biology Brain General Medicine Human brain 030104 developmental biology medicine.anatomical_structure chemistry biology.protein collision-induced dissociation gangliosides human cerebrospinal fluid ion mobility separation/spectrometry mass spectrometry (IMS MS) Biomarkers |
| DOI: | 10.1016/j.biochi.2019.12.008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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