Potentials of modern mass spectrometric methods in neuroscience research and neuropathologic diagnosis: mapping and sequencing of brain gangliosides (CROSBI ID 495614)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | domaća recenzija
Podaci o odgovornosti
Vukelić, Željka ; Metelmann-Strupat, Wolfgang ; Zamfir, Alina ; Bindila, Laura ; Froesch, Martin ; Peter-Katalinić, Jasna
engleski
Potentials of modern mass spectrometric methods in neuroscience research and neuropathologic diagnosis: mapping and sequencing of brain gangliosides
Introduction. Gangliosides, sialylated glycosphingolipids (GSLs), are plasma-membrane components highly abundant in the central nervous system. They participate in cell-to-cell recognition/communication and cell signaling. Ganglioside composition is species- and cell type-specific and specifically changes during brain development, maturation, aging and disease/neurodegeneration. Therefore, gangliosides could be used as valuable tissue stage- and/or diagnostic markers and potentially as therapeutic agents. To define the exact structure-to-function interrelationship for each species a detailed and unambiguous compositional mapping and structural elucidation of individual components is of crucial necessity. Current sophisticated mass spectrometric (MS) techniques, characterized by high sensitivity, high resolution and accuracy, offer a potent background to develop fast and sensitive strategies for detailed composition/structure analysis of various biomolecules. Such successful strategies using the negative ion mode nano-electrospray ionization quadrupole time-of-flight mass spectrometry ((-)nano-ESI-QTOF MS) have been recently established in our laboratory for screening and sequencing of gangliosides and other types of GSLs in a complex native mixture using combined data from MS1 and low energy collision-induced dissociation (CID) tandem MS (MS/MS) ; 1-3 similar approaches using nano-ESI Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS)4 are currently under optimization. Materials and Methods. Native mixtures of brain gangliosides, analyzed in this study, were isolated from anencephalic cerebral remnant (AnCR ; 37 g.w.), an age-matched normal fetal cerebrum (NFC), and an adult human cerebrum (42 y.). MS experiments were performed on a QTOF mass spectrometer (Micromass, Manchester, UK) fitted with a Micromass nanoelectrospray (nano-ESI) source and on an Apex II FT-ICR mass spectrometer equipped with a 9.4 T superconducting magnet (Bruker Daltonik, Bremen, Germany), interfaced with a nano-ESI source. Results. Presented results demonstrate complexity of the sample composition/structure related data that could be obtained from single optimized experiment using either nano-ESI-QTOF MS or nano-ESI-FT-ICR MS. Comparative nano-ESI-QTOF MS1 analysis of complex native ganglioside mixtures from AnCR and age matched NFC showed obvious differences concerning abundance of some minor species. From the tandem MS/MS analysis of detected molecular ions it was, even in cases of extremely low ion abundance (for example GP1), possible to elucidate a complete carbohydrate sequences including attachment sites of sialic acid residues as well as the type of ceramide residue. The Nano-ESI-FT-ICR MS introduced for the first time to the analysis of complex native mixture from adult human brain showed very detailed ganglioside composition ; due to higher sensitivity for minor ganglioside species the obtained pattern was even more complex than detected by nano-ESI-QTOF MS. Conclusions. Optimized nano-ESI-QTOF and nano-ESI-FT-ICR MS strategies for screening and structural analysis of gangliosides provide a significant impact to the understanding of functional and pathological implications of gangliosides in nervous system and could be helpful in defining potential diagnostic markers. 1. Metelmann, W., Vukelić, Ž., Peter-Katalinić, J., J Mass Spectrom. 2001, 36, 21-29 2. Vukelić, Ž., Metelmann, W., Müthing, J., Kos M., Peter-Katalinić J. Biol. Chem. 2001, 38, 259-274 3. Zamfir, A., Vukelić, Ž., Peter-Katalinić, J., Electrophoresis. 2002, 23, 2894-2903 4. Froesch, M., Bindila, L., Zamfir, A., Peter-Katalinić, J. Rapid Commun. Mass Spectrom. (in press)
Gangliosides; mass spectrometric (MS) techniques; composition/structure analysis
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Podaci o prilogu
108-109-x.
2003.
objavljeno
Podaci o matičnoj publikaciji
Neurologia Croatica, Suppl.4, Book of Abstracts, The First Croatian Congress of Neuroscience
Bulat, Marin ; Ivkić, Goran ; Judaš, Miloš ; Klarica, Marijan ; Kostović, Ivica ; Šimić, Goran ; Petravić, D.
Zagreb: Neurologia Croatica
Podaci o skupu
The First Croatian Congress of Neuroscience
poster
21.11.2003-22.11.2003
Zagreb, Hrvatska