Analysis of human hippocampus gangliosides by fully-automated chip-based nanoelectrospray tandem mass spectrometry

Vukelić, Željka; Zarei, Mostafa; Peter‐Katalinić, Jasna; Zamfir, Alina D.

doi:10.1016/j.chroma.2006.05.033

Cited by 47 publications

(38 citation statements)

References 39 publications

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“…However, for the complete structural analysis of GSL, more sophisticated and advanced techniques are required. Presently, mass spectrometry (MS), intensively exploited for lipid characterization [32,33], is considered also one of the most precise and sensitive analytical methods in the detection and structural identification of different ganglioside species [34][35][36][37][38][39][40][41].…”

Section: Introductionmentioning

confidence: 99%

Assessment of the Molecular Expression and Structure of Gangliosides in Brain Metastasis of Lung Adenocarcinoma by an Advanced Approach Based on Fully Automated Chip-Nanoelectrospray Mass Spectrometry

Zamfir

Serb

Vukeli

et al. 2011

J. Am. Soc. Mass Spectrom.

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Gangliosides (GGs), sialic acid-containing glycosphingolipids, are known to be involved in the invasive/metastatic behavior of brain tumor cells. Development of modern methods for determination of the variations in GG expression and structure during neoplastic cell transformation is a priority in the field of biomedical analysis. In this context, we report here on the first optimization and application of chip-based nanoelectrospray (NanoMate robot) mass spectrometry (MS) for the investigation of gangliosides in a secondary brain tumor. In our work a native GG mixture extracted and purified from brain metastasis of lung adenocarcinoma was screened by NanoMate robot coupled to a quadrupole time-of-flight MS. A native GG mixture from an agematched healthy brain tissue, sampled and analyzed under identical conditions, served as a control. Comparative MS analysis demonstrated an evident dissimilarity in GG expression in the two tissue types. Brain metastasis is characterized by many species having a reduced Nacetylneuraminic acid (Neu5Ac) content, however, modified by fucosylation or O-acetylation such as Fuc-GM4, Fuc-GM3, di-O-Ac-GM1, O-Ac-GM3. In contrast, healthy brain tissue is dominated by longer structures exhibiting from mono-to hexasialylated sugar chains. Also, significant differences in ceramide composition were discovered. By tandem MS using collisioninduced dissociation at low energies, brain metastasis-associated GD3 (d18:1/18:0) species as well as an uncommon Fuc-GM1 (d18:1/18:0) detected in the normal brain tissue could be structurally characterized. The novel protocol was able to provide a reliable compositional and structural characterization with high analysis pace and at a sensitivity situated in the fmol range.

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Section: Introductionmentioning

confidence: 99%

Assessment of the Molecular Expression and Structure of Gangliosides in Brain Metastasis of Lung Adenocarcinoma by an Advanced Approach Based on Fully Automated Chip-Nanoelectrospray Mass Spectrometry

Zamfir

Serb

Vukeli

et al. 2011

J. Am. Soc. Mass Spectrom.

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“…Obtained structures from Table 1 were compared with previously reported (manually interpreted) ganglioside analysis of human fetal hippocampi (15 and 17 g.w.). 25 The brain samples showed high resemblance in general GG pattern, sharing all common ganglioside species characteristically present in fetal human brain (GM3, GM2, GD3, GD2, GM1, GD1, GT1). Signals with highest intensity in all brain tissues samples correspond to GD1 (d18:1/ 18:0) and GT1 (d18:1/18:0).…”

Section: Fetal Human Brain Gangliosides Analysismentioning

confidence: 99%

“…44 Altogether, 34 different ganglioside structures, 5 sulfatides, and 1 neutral GSL species were characterized in the analyzed mixture from adult human brain cortex, which is 19 structures more than previously identified (manually interpreted) in ganglioside mixture isolated from adult human hippocampus (20 years). 25 …”

Section: Adult Human Brain Ganglioside Analysismentioning

confidence: 99%

“…16,17,[19][20][21][22][23][24] Although MS and tandem MS approaches to generate spectral data have been successful, data analysis and interpretation still remains demanding and time consuming. Employment of MS for comparative compositional and structural characterization of complex GSL mixtures isolated from tissues and other biological material 11,15,17,[24][25][26][27][28][29] demands interpretation and comparison of large amount of data, in order to investigate their involvement/role and biomarker potential in physiological/biological processes in health and diseases. Therefore, researchers in glycolipidomics and biomedicine fields seek for assistance of applicable software tools.…”

Section: Introductionmentioning

confidence: 99%

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Database and data analysis application for structural characterization of gangliosides and sulfated glycosphingolipids by negative ion mass spectrometry

Rožman

Fabris

Mrla

et al. 2014

Carbohydrate Research

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Gangliosides and sulfated glycosphingolipids, as building and functional components of animal cell mem-branes, participate in cell-to-cell interactions and signaling, but also in changes of cell architecture due to different pathophysiological events. In order to enable higher throughput and to facilitate structural characterization of gangliosides/sulfo-glycosphingolipids (GSL) and their neutral GSL counterparts by negative ion mass spectrometry (MS) and tandem MS techniques, a database and data analysis applica-tion have been developed. In silico developed glycosphingolipid database considers a high diversity of ceramide compositions, several sialic acid types (N-acetylneuraminic acid, N-glycolylneuraminic acid and 2-keto-3-deoxynononic acid) as well as possible additional substitutions/modifications of glycosphingolipids, such as O-acetylation, de-N-acetylation, fucosylation, glucuronosylation, sulfation, attachment of repeating terminal hexose-N-acetylhexosamine-(Hex-HexNAc-) 1-6 extension, and possi-ble lactone forms. Data analysis application, named GSL-finder, enables correlation of negative ion MS and/or low-energy tandem MS spectra with the database structures. The GSLdatabase construction and the GSL-finder application searching rules are explained. Validation conducted on GD1a fraction as well as on complex mixtures of native gangliosides isolated from different mammalian brain tissues (human fetal and adult brain, and calf brain tissue) demonstrated agreement with previous studies. Plain, fast, and automated routine for structural characterization of gangliosides/sulfated glycosphingolipids and their neutral GSL counterparts described here could facilitate and improve mass spectrometric analysis of complex glycosphingolipid mixtures originating from variety of normal and pathological biomaterial, where it is known that distinctive changes in glycosphingolipid composition occur.

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“…Lipid MS uses various ionization methods [e.g., electrospray ionization, (ESI) and matrix-assisted laserdesorption ionization (MALDI)] combined with triple quadrupole or tandem quadrupole-linear ion trap mass analyzers for MS/MS and MS n (10), respectively, or for higher mass accuracy, time-of-flight (11) or Fourier transform instruments (12,13). The combination of MS with liquid chromatography (10,14), thin-layer chromatography (12,15), and automated microfluidic "chip"-based devices (16) has been successful in meeting difficult analytical challenges posed by the presence of contaminants that suppress ionization, isomeric species, etc. Unfortunately, a major limitation for quantitative analysis is that certified internal standards are only available for the "core" sphingolipids (Avanti Polar Lipids, Alabaster, AL).…”

Section: Sphingolipidomic Analysismentioning

confidence: 99%

Sphingolipidomics: a valuable tool for understanding the roles of sphingolipids in biology and disease

Merrill

Stokes

Momin

et al. 2009

Journal of Lipid Research

132

100

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The sphingolipidome is the portion of the lipidome that encompasses all sphingoid bases and their derivatives. Whereas the most studied sphingoid base is sphingosine [(2S,3R,4E)-2-aminooctadecene-1,3-diol], mammals have dozens of structural variants, and hundreds of additional types have been found in other eukaryotic organisms and some bacteria and viruses. Multiplying these figures by the N-acylderivatives ("ceramides") and the more than 500 phospho-and glyco-headgroups places the number of discrete molecular species in the tens of thousands or higher. Structure-specific, quantitative information about a growing fraction of the sphingolipidome can now be obtained using various types of chromatography coupled with tandem mass spectrometry, and application of these methods is producing many surprises regarding sphingolipid structure, metabolism, and function. Such large data sets can be difficult to interpret, but the development of tools that display results from genomic and lipidomic studies in a pathway relational, nodal, context can make it easier for investigators to deal with this complexity.

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Analysis of human hippocampus gangliosides by fully-automated chip-based nanoelectrospray tandem mass spectrometry

Cited by 47 publications

References 39 publications

Assessment of the Molecular Expression and Structure of Gangliosides in Brain Metastasis of Lung Adenocarcinoma by an Advanced Approach Based on Fully Automated Chip-Nanoelectrospray Mass Spectrometry

Assessment of the Molecular Expression and Structure of Gangliosides in Brain Metastasis of Lung Adenocarcinoma by an Advanced Approach Based on Fully Automated Chip-Nanoelectrospray Mass Spectrometry

Database and data analysis application for structural characterization of gangliosides and sulfated glycosphingolipids by negative ion mass spectrometry

Sphingolipidomics: a valuable tool for understanding the roles of sphingolipids in biology and disease

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