Hepatic Topology of Glycosphingolipids in Schistosoma mansoni-Infected Hamsters

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   Varki, Ajit

   Glycobiology (2017), 27 (1), 3-49CODEN: GLYCE3; ISSN:1460-2423. (Oxford University Press)

   Simple and complex carbohydrates (glycans) have long been known to play major metabolic, structural and phys. roles in biol. systems. Targeted microbial binding to host glycans has also been studied for decades. But such biol. roles can only explain some of the remarkable complexity and organismal diversity of glycans in nature. Reviewing the subject about two decades ago, one could find very few clear-cut instances of glycan-recognition-specific biol. roles of glycans that were of intrinsic value to the organism expressing them. In striking contrast there is now a profusion of examples, such that this updated review cannot be comprehensive. Instead, a historical overview is presented, broad principles outlined and a few examples cited, representing diverse types of roles, mediated by various glycan classes, in different evolutionary lineages. What remains unchanged is the fact that while all theories regarding biol. roles of glycans are supported by compelling evidence, exceptions to each can be found. In retrospect, this is not surprising. Complex and diverse glycans appear to be ubiquitous to all cells in nature, and essential to all life forms. Thus, >3 billion years of evolution consistently generated organisms that use these mols. for many key biol. roles, even while sometimes coopting them for minor functions. In this respect, glycans are no different from other major macromol. building blocks of life (nucleic acids, proteins and lipids), simply more rapidly evolving and complex. It is time for the diverse functional roles of glycans to be fully incorporated into the mainstream of biol. sciences.
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   Aerts, J. M. F. G.; Artola, M.; van Eijk, M.; Ferraz, M. J.; Boot, R. G. Glycosphingolipids and Infection. Potential New Therapeutic Avenues. Front. Cell Dev. Biol. 2019, 7, 324,  DOI: 10.3389/fcell.2019.00324

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   Glycosphingolipids and Infection. Potential New Therapeutic Avenues

   Aerts Johannes M F G; Artola M; van Eijk M; Ferraz M J; Boot R G

   Frontiers in cell and developmental biology (2019), 7 (), 324 ISSN:2296-634X.

   Glycosphingolipids (GSLs), the main topic of this review, are a subclass of sphingolipids. With their glycans exposed to the extracellular space, glycosphingolipids are ubiquitous components of the plasma membrane of cells. GSLs are implicated in a variety of biological processes including specific infections. Several pathogens use GSLs at the surface of host cells as binding receptors. In addition, lipid-rafts in the plasma membrane of host cells may act as platform for signaling the presence of pathogens. Relatively common in man are inherited deficiencies in lysosomal glycosidases involved in the turnover of GSLs. The associated storage disorders (glycosphingolipidoses) show lysosomal accumulation of substrate(s) of the deficient enzyme. In recent years compounds have been identified that allow modulation of GSLs levels in cells. Some of these agents are well tolerated and already used to treat lysosomal glycosphingolipidoses. This review summarizes present knowledge on the role of GSLs in infection and subsequent immune response. It concludes with the thought to apply glycosphingolipid-lowering agents to prevent and/or combat infections.
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   Spengler, B.; Hubert, M.; Kaufmann, R. MALDI ion imaging and biological ion imaging with a new scanning UV-laser microprobe. Proceedings of the 42nd Annual Conference on Mass Spectrometry and Allied Topics , 1994; Vol. 1040.

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   Koestler, M.; Kirsch, D.; Hester, A.; Leisner, A.; Guenther, S.; Spengler, B. A high-resolution scanning microprobe matrix-assisted laser desorption/ionization ion source for imaging analysis on an ion trap/Fourier transform ion cyclotron resonance mass spectrometer. Rapid Commun. Mass Spectrom. 2008, 22, 3275– 3285,  DOI: 10.1002/rcm.3733

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   A high-resolution scanning microprobe matrix-assisted laser desorption/ionization ion source for imaging analysis on an ion trap/Fourier transform ion cyclotron resonance mass spectrometer

   Koestler, Martin; Kirsch, Dieter; Hester, Alfons; Leisner, Arne; Guenther, Sabine; Spengler, Bernhard

   Rapid Communications in Mass Spectrometry (2008), 22 (20), 3275-3285CODEN: RCMSEF; ISSN:0951-4198. (John Wiley & Sons Ltd.)

   A new scanning microprobe matrix-assisted laser desorption/ionization (SMALDI) ion source for high spatial resoln. was developed for linear ion trap and Fourier transform ICR mass spectrometry (FT-ICR-MS). The source is fully compatible with com. ion trap flanges (such as the LTQ series, Thermo Fisher Scientific). The source is designed for atm. pressure (AP) operation but is also suitable for mid-pressure operation. The AP mode is esp. useful for studying volatile compds. The source can be interchanged with other ion sources within a minute when operated in the AP mode. Combining high-lateral resoln. MALDI imaging with high mass resoln. and high mass accuracy mass spectrometry, available in the FT-ICR mode, provides a new quality of anal. information, e.g. from biol. samples. First results obtained with the new ion source demonstrate a max. lateral resoln. of 0.6 by 0.5 μm. Depending on the limit of detection of the chosen mass analyzer, however, the size of the focus had to be enlarged to a diam. of up to 8 μm in the FT-ICR mode, to create enough ions for detection. Mass spectra acquired for anal. imaging were obtained from single laser pulses per pixel in all the expts. This mode allows one to study biol. thin sections with desorption focus diams. in the micrometer range, known to cause complete evapn. of material under the laser focus with a very limited no. of laser pulses. As a 1st example, peptide samples deposited in microstructures were studied with the new setup. A high quality and validity of the acquired images were obtained in the ion trap mode due to the low limit of detection. High mass resoln. and accuracy but poorer image quality were obtained in the ICR mode due to the lower detection sensitivity of the ICR detector.
5. 5

   Bien, T.; Perl, M.; Machmüller, A. C.; Nitsche, U.; Conrad, A.; Johannes, L.; Müthing, J.; Soltwisch, J.; Janssen, K.-P.; Dreisewerd, K. MALDI-2 Mass Spectrometry and Immunohistochemistry Imaging of Gb3Cer, Gb4Cer, and Further Glycosphingolipids in Human Colorectal Cancer Tissue. Anal. Chem. 2020, 92, 7096– 7105,  DOI: 10.1021/acs.analchem.0c00480

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   MALDI-2 Mass Spectrometry and Immunohistochemistry Imaging of Gb3Cer, Gb4Cer, and Further Glycosphingolipids in Human Colorectal Cancer Tissue

   Bien, Tanja; Perl, Markus; Machmueller, Andrea C.; Nitsche, Ulrich; Conrad, Anja; Johannes, Ludger; Muething, Johannes; Soltwisch, Jens; Janssen, Klaus-Peter; Dreisewerd, Klaus

   Analytical Chemistry (Washington, DC, United States) (2020), 92 (10), 7096-7105CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)

   The main cellular receptors of Shiga toxins (Stxs), the neutral glycosphingolipids (GSLs), globotriaosylceramide (Gb3Cer/CD77) and globotetraosylceramide (Gb4Cer), are significantly upregulated in about half of the human colorectal carcinomas (CRC) and in other cancers. Therefore, conjugates exploiting the Gb3Cer/Gb4Cer-binding B subunit of Stx (StxB) have attracted great interest for both diagnostic and adjuvant therapeutic interventions. Moreover, fucosylated GSLs were recognized as potential tumor-assocd. targets. One obstacle to a broader use of these receptor/ligand systems is that the contribution of specific GSLs to tumorigenesis, in particular, in the context of an altered lipid metab., is only poorly understood. A second is that also nondiseased organs (e.g., kidney) and blood vessels can express high levels of certain GSLs, not least Gb3Cer/Gb4Cer. Here, we used, in a proof-of-concept study, matrix-assisted laser desorption/ionization mass spectrometry imaging combined with laser-induced postionization (MALDI-2-MSI) to simultaneously visualize the distribution of several Gb3Cer/Gb4Cer lipoforms and those of related GSLs (e.g., Gb3Cer/Gb4Cer precursors and fucosylated GSLs) in tissue biopsies from three CRC patients. Using MALDI-2 and StxB-based immunofluorescence microscopy, Gb3Cer and Gb4Cer were mainly found in dedifferentiated tumor cell areas, tumor stroma, and tumor-infiltrating blood vessels. Notably, fucosylated GSL such as Fuc-(n)Lc4Cer generally showed a highly localized expression in dysplastic glands and indian file-like cells infiltrating adipose tissue. Our "mol. histol." approach could support stratifying patients for intratumoral GSL expression to identify an optimal therapeutic strategy. The improved chem. coverage by MALDI-2 can also help to improve our understanding of the mol. basis of tumor development and GSL metab.
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   Atmospheric pressure MALDI mass spectrometry imaging of tissues and cells at 1.4-μm lateral resolution

   Kompauer, Mario; Heiles, Sven; Spengler, Bernhard

   Nature Methods (2017), 14 (1), 90-96CODEN: NMAEA3; ISSN:1548-7091. (Nature Publishing Group)

   We report an atm. pressure (AP) matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) setup with a lateral resoln. of 1.4μm, a mass resoln. greater than 100,000, and accuracy below ±2 p.p.m. We achieved this by coupling a focusing objective with a numerical aperture (NA) of 0.9 at 337 nm and a free working distance of 18 mm in coaxial geometry to an orbitrap mass spectrometer and optimizing the matrix application. We demonstrate improvement in image contrast, lateral resoln., and ion yield per unit area compared with a state-of-the-art com. MSI source. We show that our setup can be used to detect metabolites, lipids, and small peptides, as well as to perform tandem MS expts. with 1.5-μm2 sampling areas. To showcase these capabilities, we identified subcellular lipid, metabolite, and peptide distributions that differentiate, for example, cilia and oral groove in Paramecium caudatum.
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   Wiedemann, K. R.; Peter Ventura, A.; Gerbig, S.; Roderfeld, M.; Quack, T.; Grevelding, C. G.; Roeb, E.; Spengler, B. Changes in the lipid profile of hamster liver after Schistosoma mansoni infection, characterized by mass spectrometry imaging and LC-MS/MS analysis. Anal. Bioanal. Chem. 2022, 414, 3653– 3665,  DOI: 10.1007/s00216-022-04006-6

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    Zhang, T.; de Waard, A. A.; Wuhrer, M.; Spaapen, R. M. The Role of Glycosphingolipids in Immune Cell Functions. Front. Immunol. 2019, 10, 90,  DOI: 10.3389/fimmu.2019.00090

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    The role of glycosphingolipids in immune cell functions

    Zhang, Tao; de Waard, Antonius A.; Wuhrer, Manfred; Spaapen, Robbert M.

    Frontiers in Immunology (2019), 10 (), 90CODEN: FIRMCW; ISSN:1664-3224. (Frontiers Media S.A.)

    A review. Glycosphingolipids (GSLs) exhibit a variety of functions in cellular differentiation and interaction. Also, they are known to play a role as receptors in pathogen invasion. A less well-explored feature is the role of GSLs in immune cell function which is the subject of this review article. Here we summarize knowledge on GSL expression patterns in different immune cells. We review the changes in GSL expression during immune cell development and differentiation, maturation, and activation. Furthermore, we review how immune cell GSLs impact membrane organization, mol. signaling, and trans-interactions in cellular cross-talk. Another aspect covered is the role of GSLs as targets of antibody-based immunity in cancer. We expect that recent advances in anal. and genome editing technologies will help in the coming years to further our knowledge on the role of GSLs as modulators of immune cell function.
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    Dissociation of the insulin receptor and caveolin-1 complex by ganglioside GM3 in the state of insulin resistance

    Kabayama, Kazuya; Sato, Takashige; Saito, Kumiko; Loberto, Nicoletta; Prinetti, Alessandro; Sonnino, Sandro; Kinjo, Masataka; Igarashi, Yasuyuki; Inokuchi, Jin-ichi

    Proceedings of the National Academy of Sciences of the United States of America (2007), 104 (34), 13678-13683CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)

    Membrane microdomains (lipid rafts) are now recognized as crit. for proper compartmentalization of insulin signaling. We previously demonstrated that, in adipocytes in a state of TNFα-induced insulin resistance, the inhibition of insulin metabolic signaling and the elimination of insulin receptors (IR) from the caveolae microdomains were assocd. with an accumulation of the ganglioside GM3. To gain insight into mol. mechanisms behind interactions of IR, caveolin-1 (Cav1), and GM3 in adipocytes, we have performed immunopptns., crosslinking studies of IR and GM3, and live cell studies using total internal reflection fluorescence microscopy and fluorescence recovery after photobleaching techniques. We found that (i) IR form complexes with Cav1 and GM3 independently; (i) in GM3-enriched membranes the mobility of IR is increased by dissocn. of the IR-Cav1 interaction; and (ii,) the lysine residue localized just above the transmembrane domain of the IR 3-subunit is essential for the interaction of IR with GM3. Because insulin metabolic signal transduction in adipocytes is known to be critically dependent on caveolae, we propose a pathol. feature of insulin resistance in adipocytes caused by dissocn. of the IR-Cav1 complex by the interactions of IR with GM3 in microdomains.
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    Barrientos, R. C.; Zhang, Q. Recent advances in the mass spectrometric analysis of glycosphingolipidome - A review. Anal. Chim. Acta 2020, 1132, 134– 155,  DOI: 10.1016/j.aca.2020.05.051

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    Recent advances in the mass spectrometric analysis of glycosphingolipidome - A review

    Barrientos, Rodell C.; Zhang, Qibin

    Analytica Chimica Acta (2020), 1132 (), 134-155CODEN: ACACAM; ISSN:0003-2670. (Elsevier B.V.)

    A review. Aberrant expression of glycosphingolipids has been implicated in a myriad of diseases, but the authors' understanding of the strucural diversity, spatial distribution, and biol. function of this class of biomols. remains limited. These challenges partly stem from a lack of sensitive tools that can detect, identify, and quantify glycosphingolipids at the mol. level. Mass spectrometry has emerged as a powerful tool poised to address most of these challenges. Here, the authors review the recent developments in anal. glycosphingolipidomics with an emphasis on sample prepn., mass spectrometry and tandem mass spectrometry-based structural characterization, label-free and labeling-based quantification. The authors also discuss the nomenclature of glycosphingolipids, and emerging technologies like ion mobility spectrometry in differentiation of glycosphingolipid isomers. The intrinsic advantages and shortcomings of each method are carefully critiqued in line with an individual's research goals. Finally, future perspectives on anal. sphingolipidomics are stated, including a need for novel and more sensive methods in isomer sepn., low abundance species detection, and profiling the spatial distribution of glycosphingolipid mol. species in cells and tissues using imaging mass spectrometry.
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    Hořejší, K.; Jirásko, R.; Chocholoušková, M.; Wolrab, D.; Kahoun, D.; Holčapek, M. Comprehensive Identification of Glycosphingolipids in Human Plasma Using Hydrophilic Interaction Liquid Chromatography-Electrospray Ionization Mass Spectrometry. Metabolites 2021, 11, 140,  DOI: 10.3390/metabo11030140

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    Roderfeld, M.; Padem, S.; Lichtenberger, J.; Quack, T.; Weiskirchen, R.; Longerich, T.; Schramm, G.; Churin, Y.; Irungbam, K.; Tschuschner, A.; Windhorst, A.; Grevelding, C. G.; Roeb, E. Schistosoma mansoni Egg-Secreted Antigens Activate Hepatocellular Carcinoma-Associated Transcription Factors c-Jun and STAT3 in Hamster and Human Hepatocytes. Hepatology 2020, 72, 626– 641,  DOI: 10.1002/hep.30192

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    Weglage, J.; Wolters, F.; Hehr, L.; Lichtenberger, J.; Wulz, C.; Hempel, F.; Baier, A.; Quack, T.; Köhler, K.; Longerich, T.; Schramm, G.; Irungbam, K.; Mueller, H.; von Buelow, V.; Tschuschner, A.; Odenthal, M.; Drebber, U.; Arousy, M. E.; Ramalho, L. N. Z.; Bankov, K.; Wild, P.; Pons-Kühnemann, J.; Tschammer, J.; Grevelding, C. G.; Roeb, E.; Roderfeld, M. Schistosoma mansoni eggs induce Wnt/β-catenin signaling and activate the protooncogene c-Jun in human and hamster colon. Sci. Rep. 2020, 10, 22373,  DOI: 10.1038/s41598-020-79450-4

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    Kompauer, M.; Heiles, S.; Spengler, B. Autofocusing MALDI mass spectrometry imaging of tissue sections and 3D chemical topography of nonflat surfaces. Nat. Methods 2017, 14, 1156– 1158,  DOI: 10.1038/nmeth.4433

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    Autofocusing MALDI mass spectrometry imaging of tissue sections and 3D chemical topography of nonflat surfaces

    Kompauer, Mario; Heiles, Sven; Spengler, Bernhard

    Nature Methods (2017), 14 (12), 1156-1158CODEN: NMAEA3; ISSN:1548-7091. (Nature Research)

    We describe an atm. pressure matrix-assisted laser desorption-ionization mass spectrometry imaging system that uses long-distance laser triangulation on a micrometer scale to simultaneously obtain topog. and mol. information from 3D surfaces. We studied the topog. distribution of compds. on irregular 3D surfaces of plants and parasites, and we imaged nonplanar tissue sections with high lateral resoln., thereby eliminating height-related signal artifacts.
23. 23

    Paschke, C.; Leisner, A.; Hester, A.; Maass, K.; Guenther, S.; Bouschen, W.; Spengler, B. Mirion–a software package for automatic processing of mass spectrometric images. J. Am. Soc. Mass Spectrom. 2013, 24, 1296– 1306,  DOI: 10.1007/s13361-013-0667-0

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    Mirion--A Software Package for Automatic Processing of Mass Spectrometric Images

    Paschke, C.; Leisner, A.; Hester, A.; Maass, K.; Guenther, S.; Bouschen, W.; Spengler, B.

    Journal of the American Society for Mass Spectrometry (2013), 24 (8), 1296-1306CODEN: JAMSEF; ISSN:1044-0305. (Springer)

    Mass spectrometric imaging (MSI) techniques are of growing interest for the Life Sciences. In recent years, the development of new instruments employing ion sources that are tailored for spatial scanning allowed the acquisition of large data sets. A subsequent data processing, however, is still a bottleneck in the anal. process, as a manual data interpretation is impossible within a reasonable time frame. The transformation of mass spectrometric data into spatial distribution images of detected compds. turned out to be the most appropriate method to visualize the results of such scans, as humans are able to interpret images faster and easier than plain nos. Image generation, thus, is a time-consuming and complex yet very efficient task. The free software package "Mirion," presented allows the handling and anal. of data sets acquired by mass spectrometry imaging. Mirion can be used for image processing of MSI data obtained from many different sources, as it uses the HUPO-PSI-based std. data format imzML, which is implemented in the proprietary software of most of the mass spectrometer companies. Different graphical representations of the recorded data are available. Furthermore, automatic calcn. and overlay of mass spectrometric images promotes direct comparison of different analytes for data evaluation. The program also includes tools for image processing and image anal.
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    Vajn, K.; Viljetić, B.; Degmečić, I. V.; Schnaar, R. L.; Heffer, M. Differential distribution of major brain gangliosides in the adult mouse central nervous system. PLoS One 2013, 8, e75720  DOI: 10.1371/journal.pone.0075720

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    Differential distribution of major brain gangliosides in the adult mouse central nervous system

    Vajn, Katarina; Viljetic, Barbara; Degmecic, Ivan Veceslav; Schnaar, Ronald L.; Heffer, Marija

    PLoS One (2013), 8 (9), e75720CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)

    Gangliosides - sialic acid-bearing glycolipids - are major cell surface determinants on neurons and axons. The same four closely related structures, GM1, GD1a, GD1b and GT1b, comprise the majority of total brain gangliosides in mammals and birds. Gangliosides regulate the activities of proteins in the membranes in which they reside, and also act as cell-cell recognition receptors. Understanding the functions of major brain gangliosides requires knowledge of their tissue distribution, which has been accomplished in the past using biochem. and immunohistochem. methods. Armed with new knowledge about the stability and accessibility of gangliosides in tissues and new IgG-class specific monoclonal antibodies, we investigated the detailed tissue distribution of gangliosides in the adult mouse brain. Gangliosides GD1b and GT1b are widely expressed in gray and white matter. In contrast, GM1 is predominately found in white matter and GD1a is specifically expressed in certain brain nuclei/tracts. These findings are considered in relationship to the hypothesis that gangliosides GD1a and GT1b act as receptors for an important axon-myelin recognition protein, myelin-assocd. glycoprotein (MAG). Mediating axon-myelin interactions is but one potential function of the major brain gangliosides, and more detailed knowledge of their distribution may help direct future functional studies.
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    Vens-Cappell, S.; Kouzel, I. U.; Kettling, H.; Soltwisch, J.; Bauwens, A.; Porubsky, S.; Müthing, J.; Dreisewerd, K. On-Tissue Phospholipase C Digestion for Enhanced MALDI-MS Imaging of Neutral Glycosphingolipids. Anal. Chem. 2016, 88, 5595– 5599,  DOI: 10.1021/acs.analchem.6b01084

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    On-Tissue Phospholipase C Digestion for Enhanced MALDI-MS Imaging of Neutral Glycosphingolipids

    Vens-Cappell, Simeon; Kouzel, Ivan U.; Kettling, Hans; Soltwisch, Jens; Bauwens, Andreas; Porubsky, Stefan; Muething, Johannes; Dreisewerd, Klaus

    Analytical Chemistry (Washington, DC, United States) (2016), 88 (11), 5595-5599CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)

    Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can be used to simultaneously visualize the lateral distribution of different lipid classes in tissue sections, but the applicability of the method to real-life samples is often limited by ion suppression effects. In particular, the presence of abundant phosphatidylcholines (PCs) can reduce the ion yields for all other lipid species in pos. ion mode measurements. Here, we used on-tissue treatment with buffer-free phospholipase C (PLC) to near-quant. degrade PCs in fresh-frozen tissue sections. The ion signal intensities of mono-, di-, and oligohexosylceramides were enhanced by up to 10-fold. In addn., visualization of Shiga toxin receptor globotriaosylceramide (Gb3Cer) in the kidneys of wild-type and α-galactosidase A-knockout (Fabry) mice was possible at about ten micrometer resoln. Importantly, the PLC treatment did not decrease the high lateral resoln. of the MS imaging anal.
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    Kirsch, S.; Müthing, J.; Peter-Katalinić, J.; Bindila, L. On-line nano-HPLC/ESI QTOF MS monitoring of α2–3 and α2–6 sialylation in granulocyte glycosphingolipidome. Biol. Chem. 2009, 390, 657– 672,  DOI: 10.1515/BC.2009.066

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    Katajamaa, M.; Miettinen, J.; Oresic, M. MZmine: toolbox for processing and visualization of mass spectrometry based molecular profile data. Bioinformatics 2006, 22, 634– 636,  DOI: 10.1093/bioinformatics/btk039

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    MZmine: toolbox for processing and visualization of mass spectrometry based molecular profile data

    Katajamaa, Mikko; Miettinen, Jarkko; Oresic, Matej

    Bioinformatics (2006), 22 (5), 634-636CODEN: BOINFP; ISSN:1367-4803. (Oxford University Press)

    New addnl. methods are presented for processing and visualizing mass spectrometry based mol. profile data, implemented as part of the recently introduced MZmine software. They include new features and extensions such as support for mzXML data format, capability to perform batch processing for large no. of files, support for parallel processing, new methods for calcg. peak areas using post-alignment peak picking algorithm and implementation of Sammon's mapping and curvilinear distance anal. for data visualization and exploratory anal.
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    MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data

    Pluskal Tomas; Castillo Sandra; Villar-Briones Alejandro; Oresic Matej

    BMC bioinformatics (2010), 11 (), 395 ISSN:.

    BACKGROUND: Mass spectrometry (MS) coupled with online separation methods is commonly applied for differential and quantitative profiling of biological samples in metabolomic as well as proteomic research. Such approaches are used for systems biology, functional genomics, and biomarker discovery, among others. An ongoing challenge of these molecular profiling approaches, however, is the development of better data processing methods. Here we introduce a new generation of a popular open-source data processing toolbox, MZmine 2. RESULTS: A key concept of the MZmine 2 software design is the strict separation of core functionality and data processing modules, with emphasis on easy usability and support for high-resolution spectra processing. Data processing modules take advantage of embedded visualization tools, allowing for immediate previews of parameter settings. Newly introduced functionality includes the identification of peaks using online databases, MSn data support, improved isotope pattern support, scatter plot visualization, and a new method for peak list alignment based on the random sample consensus (RANSAC) algorithm. The performance of the RANSAC alignment was evaluated using synthetic datasets as well as actual experimental data, and the results were compared to those obtained using other alignment algorithms. CONCLUSIONS: MZmine 2 is freely available under a GNU GPL license and can be obtained from the project website at: http://mzmine.sourceforge.net/. The current version of MZmine 2 is suitable for processing large batches of data and has been applied to both targeted and non-targeted metabolomic analyses.
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    Tyanova, S.; Temu, T.; Sinitcyn, P.; Carlson, A.; Hein, M. Y.; Geiger, T.; Mann, M.; Cox, J. The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat. Methods 2016, 13, 731– 740,  DOI: 10.1038/nmeth.3901

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    The Perseus computational platform for comprehensive analysis of (prote)omics data

    Tyanova, Stefka; Temu, Tikira; Sinitcyn, Pavel; Carlson, Arthur; Hein, Marco Y.; Geiger, Tamar; Mann, Matthias; Cox, Juergen

    Nature Methods (2016), 13 (9), 731-740CODEN: NMAEA3; ISSN:1548-7091. (Nature Publishing Group)

    A main bottleneck in proteomics is the downstream biol. anal. of highly multivariate quant. protein abundance data generated using mass-spectrometry-based anal. We developed the Perseus software platform (http://www.perseus-framework.org) to support biol. and biomedical researchers in interpreting protein quantification, interaction and post-translational modification data. Perseus contains a comprehensive portfolio of statistical tools for high-dimensional omics data anal. covering normalization, pattern recognition, time-series anal., cross-omics comparisons and multiple-hypothesis testing. A machine learning module supports the classification and validation of patient groups for diagnosis and prognosis, and it also detects predictive protein signatures. Central to Perseus is a user-friendly, interactive workflow environment that provides complete documentation of computational methods used in a publication. All activities in Perseus are realized as plugins, and users can extend the software by programming their own, which can be shared through a plugin store. We anticipate that Perseus's arsenal of algorithms and its intuitive usability will empower interdisciplinary anal. of complex large data sets.
30. 30

    Fahy, E.; Subramaniam, S.; Brown, H. A.; Glass, C. K.; Merrill, A. H.; Murphy, R. C.; Raetz, C. R. H.; Russell, D. W.; Seyama, Y.; Shaw, W.; Shimizu, T.; Spener, F.; van Meer, G.; VanNieuwenhze, M. S.; White, S. H.; Witztum, J. L.; Dennis, E. A. A comprehensive classification system for lipids. J. Lipid Res. 2005, 46, 839– 861,  DOI: 10.1194/jlr.E400004-JLR200

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    A comprehensive classification system for lipids

    Fahy, Eoin; Subramaniam, Shankar; Brown, H. Alex; Glass, Christopher K.; Merrill, Alfred H., Jr.; Murphy, Robert C.; Raetz, Christian R. H.; Russell, David W.; Seyama, Yousuke; Shaw, Walter; Shimizu, Takao; Spener, Friedrich; van Meer, Gerrit; VanNieuwenhze, Michael S.; White, Stephen H.; Witztum, Joseph L.; Dennis, Edward A.

    Journal of Lipid Research (2005), 46 (5), 839-861CODEN: JLPRAW; ISSN:0022-2275. (American Society for Biochemistry and Molecular Biology, Inc.)

    Lipids are produced, transported, and recognized by the concerted actions of numerous enzymes, binding proteins, and receptors. A comprehensive anal. of lipid mols., "lipidomics," in the context of genomics and proteomics is crucial to understanding cellular physiol. and pathol.; consequently, lipid biol. has become a major research target of the postgenomic revolution and systems biol. To facilitate international communication about lipids, a comprehensive classification of lipids with a common platform that is compatible with informatics requirements has been developed to deal with the massive amts. of data that will be generated by the lipid community. As an initial step in this development, the authors divide lipids into 8 categories (fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids, and polyketides) contg. distinct classes and subclasses of mols., devise a common manner of representing the chem. structures of individual lipids and their derivs., and provide a 12 digit identifier for each unique lipid mol. The lipid classification scheme is chem. based and driven by the distinct hydrophobic and hydrophilic elements that compose the lipid. This structured vocabulary will facilitate the systematization of lipid biol. and enable the cataloging of lipids and their properties in a way that is compatible with other macromol. databases.
31. 31

    Liebisch, G.; Fahy, E.; Aoki, J.; Dennis, E. A.; Durand, T.; Ejsing, C. S.; Fedorova, M.; Feussner, I.; Griffiths, W. J.; Köfeler, H.; Merrill, A. H.; Murphy, R. C.; O’Donnell, V. B.; Oskolkova, O.; Subramaniam, S.; Wakelam, M. J. O.; Spener, F. Update on LIPID MAPS classification, nomenclature, and shorthand notation for MS-derived lipid structures. J. Lipid Res. 2020, 61, 1539– 1555,  DOI: 10.1194/jlr.S120001025

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    Update on LIPID MAPS classification, nomenclature, and shorthand notation for MS-derived lipid structures

    Liebisch, Gerhard; Fahy, Eoin; Aoki, Junken; Dennis, Edward A.; Durand, Thierry; Ejsing, Christer S.; Fedorova, Maria; Feussner, Ivo; Griffiths, William J.; Koefeler, Harald; Merrill, Alfred H., Jr.; Murphy, Robert C.; O'Donnell, Valerie B.; Oskolkova, Olga; Subramaniam, Shankar; Wakelam, Michael J. O.; Spener, Friedrich

    Journal of Lipid Research (2020), 61 (12), 1539-1555CODEN: JLPRAW; ISSN:0022-2275. (American Society for Biochemistry and Molecular Biology)

    A comprehensive and standardized system to report lipid structures analyzed by MS is essential for the communication and storage of lipidomics data. Herein, an update on both the LIPID MAPS classification system and shorthand notation of lipid structures is presented for lipid categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), and Sterols (ST). With its major changes, i.e., annotation of ring double bond equiv. and no. of oxygens, the updated shorthand notation facilitates reporting of newly delineated oxygenated lipid species as well. For standardized reporting in lipidomics, the hierarchical architecture of shorthand notation reflects the diverse structural resoln. powers provided by mass spectrometric assays. Moreover, shorthand notation is expanded beyond mammalian phyla to lipids from plant and yeast phyla. Finally, annotation of atoms is included for the use of stable isotope-labeled compds. in metabolic labeling expts. or as internal stds. This update on lipid classification, nomenclature, and shorthand annotation for lipid mass spectra is considered a std. for lipid data presentation.
32. 32

    Varki, A.; Cummings, R. D.; Aebi, M.; Packer, N. H.; Seeberger, P. H.; Esko, J. D.; Stanley, P.; Hart, G.; Darvill, A.; Kinoshita, T.; Prestegard, J. J.; Schnaar, R. L.; Freeze, H. H.; Marth, J. D.; Bertozzi, C. R.; Etzler, M. E.; Frank, M.; Vliegenthart, J. F.; Lütteke, T.; Perez, S.; Bolton, E.; Rudd, P.; Paulson, J.; Kanehisa, M.; Toukach, P.; Aoki-Kinoshita, K. F.; Dell, A.; Narimatsu, H.; York, W.; Taniguchi, N.; Kornfeld, S. Symbol Nomenclature for Graphical Representations of Glycans. Glycobiology 2015, 25, 1323– 1324,  DOI: 10.1093/glycob/cwv091

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    Symbol nomenclature for graphical representations of glycans

    Varki, Ajit; Cummings, Richard D.; Aebi, Markus; Packer, Nicole H.; Seeberger, Peter H.; Esko, Jeffrey D.; Stanley, Pamela; Hart, Gerald; Darvill, Alan; Kinoshita, Taroh; Prestegard, James J.; Schnaar, Ronald L.; Freeze, Hudson H.; Marth, Jamey D.; Bertozzi, Carolyn R.; Etzler, Marilynn E.; Frank, Martin; Vliegenthart, Johannes F. G.; Lutteke, Thomas; Perez, Serge; Bolton, Evan; Rudd, Pauline; Paulson, James; Kanehisa, Minoru; Toukach, Philip; Aoki-Kinoshita, Kiyoko F.; Dell, Anne; Narimatsu, Hisashi; York, William; Taniguchi, Naoyuki; Kornfeld, Stuart

    Glycobiology (2015), 25 (12), 1323-1324CODEN: GLYCE3; ISSN:0959-6658. (Oxford University Press)

    Symbol nomenclature for graphical representations of glycans.
33. 33

    Domon, B.; Costello, C. E. A systematic nomenclature for carbohydrate fragmentations in FAB-MS/MS spectra of glycoconjugates. Glycoconjugate J. 1988, 5, 397– 409,  DOI: 10.1007/BF01049915

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    A systematic nomenclature for carbohydrate fragmentations in FAB-MS/MS spectra of glycoconjugates

    Domon, Bruno; Costello, Catherine E.

    Glycoconjugate Journal (1988), 5 (4), 397-409CODEN: GLJOEW; ISSN:0282-0080.

    A summary of the ion types obsd. in the fast-atom-bombardment mass spectrometry (FAB-MS) and collision induced decompn. (CID) MS/MS spectra of glycoconjugates (glycosphingolipids, glycopeptides, glycosides, and carbohydrates) is presented. The variety of product ion types that arise by cleavages within the carbohydrate moieties has prompted the introduction of a systemic nomenclature to designate these ions. The proposed nomenclature has been developed primarily for FAB-MS, but can be used as well for other ionization techniques [field desorption (FD), direct chem. ionization (DCI), laser desorption/Fourier transform (LD/FT), etc.], and is applicable to spectra recorded in either the pos. or neg. ion mode during both MS and MS/MS expts. Ai, Bi, and Ci labels are used to designate fragments contg. a terminal (non-reducing end) sugar unit, whereas Xj, Yj, and Zj represent ions still contg. the aglycon (or the reducing sugar unit). Subscripts indicate the position relative to the termini analogous to the system used in peptides, and superscripts indicate cleavages within carbohydrate rings.
34. 34

    Merrill, A. H.; Sullards, M. C.; Allegood, J. C.; Kelly, S.; Wang, E. Sphingolipidomics: high-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry. Methods 2005, 36, 207– 224,  DOI: 10.1016/j.ymeth.2005.01.009

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    Sphingolipidomics: High-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry

    Merrill, Alfred H., Jr.; Sullards, M. Cameron; Allegood, Jeremy C.; Kelly, Samuel; Wang, Elaine

    Methods (San Diego, CA, United States) (2005), 36 (2), 207-224CODEN: MTHDE9; ISSN:1046-2023. (Elsevier)

    A review. Sphingolipids are a highly diverse category of compds. that serve not only as components of biol. structures but also as regulators of numerous cell functions. Because so many of the sphingolipids in a biol. system are bioactive and are often closely related structurally and metabolically (for example, complex sphingolipids <--> ceramide <--> sphingosine <--> sphingosine 1-phosphate), to understand the role(s) of sphingolipids in a given context one must conduct a "sphingolipidomic" anal. - i.e., a structure-specific and quant. measurement of all of these compds., or at least all members of a crit. subset. Liq. chromatog. tandem mass spectrometry (LC MS/MS) is currently the only technol. with the requisite structural specificity, sensitivity, quant. precision, and relatively high-throughput capabilities for such analyses in small samples (∼106 cells). This review describes a series of protocols that have been developed for the relatively rapid anal. of all of the mol. species from 3-ketosphinganines through sphingomyelins and some glycosphingolipids (including all the compds. that are presently regarded as sphingolipid "second messengers") using normal- and reverse-phase LC to sep. isometric and isobaric species (such as glucosylceramides and galactosylceramides) in combination with triple quadrupole (for MS/MS) and hybrid quadrupole-ion trap (for MS3) mass spectrometry. Also discussed are some of the issues remaining to be resolved in the anal. of the full sphingolipidome.
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    Smit, C. H.; van Diepen, A.; Nguyen, D. L.; Wuhrer, M.; Hoffmann, K. F.; Deelder, A. M.; Hokke, C. H. Glycomic Analysis of Life Stages of the Human Parasite Schistosoma mansoni Reveals Developmental Expression Profiles of Functional and Antigenic Glycan Motifs. Mol. Cell. Proteomics 2015, 14, 1750– 1769,  DOI: 10.1074/mcp.M115.048280

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    Danne-Rasche, N.; Coman, C.; Ahrends, R. Nano-LC/NSI MS Refines Lipidomics by Enhancing Lipid Coverage, Measurement Sensitivity, and Linear Dynamic Range. Anal. Chem. 2018, 90, 8093– 8101,  DOI: 10.1021/acs.analchem.8b01275

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    Nano-LC/NSI MS Refines Lipidomics by Enhancing Lipid Coverage, Measurement Sensitivity, and Linear Dynamic Range

    Danne-Rasche, Niklas; Coman, Cristina; Ahrends, Robert

    Analytical Chemistry (Washington, DC, United States) (2018), 90 (13), 8093-8101CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)

    Nano-liq. chromatog. (nLC)-nanoelectrospray (NSI) is one of the cornerstones of mass-spectrometry-based bioanalytics. Nevertheless, the application of nLC is not yet prevalent in lipid analyses. In this study, the authors established a reproducible nLC sepn. for global lipidomics and describe the merits of using such a miniaturized system for lipid analyses. In order to enable comprehensive lipid analyses that is not restricted to specific lipid classes, the authors particularly optimized sample prepn. conditions and reversed-phase sepn. parameters. The authors further benchmarked the developed nLC system to a commonly used high flow HPLC/ESI MS system in terms of lipidome coverage and sensitivity. The comparison revealed an intensity gain between 2 and 3 orders of magnitude for individual lipid classes and an increase in the linear dynamic range of up to 2 orders of magnitude. Furthermore, the anal. of the yeast lipidome using nLC/NSI resulted in more than a 3-fold gain in lipid identifications. All in all, the authors identified 447 lipids from the core phospholipid lipid classes (PA, PE, PC, PS, PG, and PI) in Saccharomyces cerevisiae.
37. 37

    Hams, E.; Aviello, G.; Fallon, P. G. The schistosoma granuloma: friend or foe?. Front. Immunol. 2013, 4, 89,  DOI: 10.3389/fimmu.2013.00089

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    The schistosoma granuloma: friend or foe?

    Hams Emily; Aviello Gabriella; Fallon Padraic G

    Frontiers in immunology (2013), 4 (), 89 ISSN:.

    Infection of man with Schistosoma species of trematode parasite causes marked chronic morbidity. Individuals that become infected with Schistosomes may develop a spectrum of pathology ranging from mild cercarial dermatitis to severe tissue inflammation, in particular within the liver and intestines, which can lead to life threatening hepatosplenomegaly. It is well established that the etiopathology during schistosomiasis is primarily due to an excessive or unregulated inflammatory response to the parasite, in particular to eggs that become trapped in various tissue. The eggs forms the foci of a classical type 2 granulomatous inflammation, characterized by an eosinophil-rich, CD4(+) T helper (Th) 2 cell dominated infiltrate with additional infiltration of alternatively activated macrophages (M2). Indeed the sequela of the type 2 perioval granuloma is marked fibroblast infiltration and development of fibrosis. Paradoxically, while the granuloma is the cause of pathology it also can afford some protection, whereby the granuloma minimizes collateral tissue damage in the liver and intestines. Furthermore, the parasite is exquisitely reliant on the host to mount a granulomatous reaction to the eggs as this inflammatory response facilitates the successful excretion of the eggs from the host. In this focused review we will address the conundrum of the S. mansoni granuloma acting as both friend and foe in inflammation during infection.
38. 38

    Llanwarne, F.; Helmby, H. Granuloma formation and tissue pathology in Schistosoma japonicum versus Schistosoma mansoni infections. Parasite Immunol. 2021, 43, e12778  DOI: 10.1111/pim.12778

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    Moné, H.; Boissier, J. Sexual biology of schistosomes. J. Adv. Parasitol. 2004, 57, 89– 189,  DOI: 10.1016/S0065-308X(04)57002-1

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    Shaw, M. K. Schistosoma mansoni: vitelline gland development in females from single sex infections. J. Helminthol. 1987, 61, 253– 259,  DOI: 10.1017/S0022149X00010117

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    Skelly, P. J.; Da’dara, A. A.; Li, X.-H.; Castro-Borges, W.; Wilson, R. A. Schistosome Feeding and Regurgitation. PLoS Pathog. 2014, 10 (8), e1004246  DOI: 10.1371/journal.ppat.1004246

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    Hayasaka, T.; Goto-Inoue, N.; Masaki, N.; Ikegami, K.; Setou, M. Application of 2,5-dihydroxyacetophenone with sublimation provides efficient ionization of lipid species by atmospheric pressure matrix-assisted laser desorption/ionization imaging mass spectrometry. Surf. Interface Anal. 2014, 46, 1219– 1222,  DOI: 10.1002/sia.5592

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    Application of 2,5-dihydroxyacetophenone with sublimation provides efficient ionization of lipid species by atmospheric pressure matrix-assisted laser desorption/ionization imaging mass spectrometry

    Hayasaka, Takahiro; Goto-Inoue, Naoko; Masaki, Noritaka; Ikegami, Koji; Setou, Mitsutoshi

    Surface and Interface Analysis (2014), 46 (12-13), 1219-1222CODEN: SIANDQ; ISSN:0142-2421. (John Wiley & Sons Ltd.)

    Imaging mass spectrometry (IMS) is a powerful tool for detecting and visualizing biomols. in tissue sections. Most IMS instruments are equipped with a high-vacuum chamber for matrix-assisted laser desorption/ionization (MALDI). However, the use of high-vacuum conditions restricts the usage of the matrix to less-volatile substances. We recently developed an atm. pressure MALDI instrument, named the 'mass microscope', to avoid this problem. The atm. pressure condition enables us to use volatile matrixes. In this study, we compared the reliability of a volatile matrix, 2,5-dihydroxyacetophenone (DHAP) with that of a conventionally used matrix, 2,5-dihydroxybenzoic acid (DHB). Compared with the results obtained with DHB, the mass spectra obtained with DHAP showed a variety of signal species in a mass region corresponding to phospholipid species in both the pos. and neg. ion modes without any matrix-derived signals. DHAP provided highly strong signals of ganglioside (GM1) species. We also compared two matrix deposition techniques for DHAP matrix: sublimation and spraying. We found that the sublimation method for applying DHAP matrix on a tissue surface can maintain ion images of lipid species, including ganglioside species only in a tissue. In contrast, the spraying method led the diffusion of GM1 species toward the outside of the tissue sections. Consequently, the sublimation method for applications of DHAP is adequate to analyze some types of lipid species including GM1 in atm. pressure MALDI IMS. Copyright © 2014 John Wiley & Sons, Ltd.
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    Jackson, S. N.; Muller, L.; Roux, A.; Oktem, B.; Moskovets, E.; Doroshenko, V. M.; Woods, A. S. AP-MALDI Mass Spectrometry Imaging of Gangliosides Using 2,6-Dihydroxyacetophenone. J. Am. Soc. Mass Spectrom. 2018, 29, 1463– 1472,  DOI: 10.1007/s13361-018-1928-8

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    AP-MALDI Mass Spectrometry Imaging of Gangliosides Using 2,6-Dihydroxyacetophenone

    Jackson, Shelley N.; Muller, Ludovic; Roux, Aurelie; Oktem, Berk; Moskovets, Eugene; Doroshenko, Vladimir M.; Woods, Amina S.

    Journal of the American Society for Mass Spectrometry (2018), 29 (7), 1463-1472CODEN: JAMSEF; ISSN:1044-0305. (Springer)

    Matrix-assisted laser/desorption ionization (MALDI) mass spectrometry imaging (MSI) is widely used as a unique tool to record the distribution of a large range of biomols. in tissues. 2,6-Dihydroxyacetophenone (DHA) matrix has been shown to provide efficient ionization of lipids, esp. gangliosides. The major drawback for DHA as it applies to MS imaging is that it sublimes under vacuum (low pressure) at the extended time necessary to complete both high spatial and mass resoln. MSI studies of whole organs. To overcome the problem of sublimation, the authors used an atm. pressure (AP)-MALDI source to obtain high spatial resoln. images of lipids in the brain using a high mass resoln. mass spectrometer. Addnl., the advantages of atm. pressure and DHA for imaging gangliosides are highlighted. The imaging of [M-H]- and [M-H2O-H]- mass peaks for GD1 gangliosides showed different distribution, most likely reflecting the different spatial distribution of GD1a and GD1b species in the brain.
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    Amaral, K. B.; Silva, T. P.; Dias, F. F.; Malta, K. K.; Rosa, F. M.; Costa-Neto, S. F.; Gentile, R.; Melo, R. C. N. Histological assessment of granulomas in natural and experimental Schistosoma mansoni infections using whole slide imaging. PLoS One 2017, 12, e0184696  DOI: 10.1371/journal.pone.0184696

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    Malta, K. K.; Silva, T. P.; Palazzi, C.; Neves, V. H.; Carmo, L. A. S.; Cardoso, S. J.; Melo, R. C. N. Changing our view of the Schistosoma granuloma to an ecological standpoint. Biol. Rev. Cambridge Philos. Soc. 2021, 96, 1404– 1420,  DOI: 10.1111/brv.12708

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    Kawanishi, K.; Dhar, C.; Do, R.; Varki, N.; Gordts, P. L. S. M.; Varki, A. Human species-specific loss of CMP- N-acetylneuraminic acid hydroxylase enhances atherosclerosis via intrinsic and extrinsic mechanisms. Proc. Natl. Acad. Sci. U.S.A. 2019, 116, 16036– 16045,  DOI: 10.1073/pnas.1902902116

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    Structure and Function of Gangliosides. Advances in Experimental Medicine and Biology; Svennerholm, L., Mandel, P., Dreyfus, H., Urban, P.-F., Eds; Springer: Boston, MA, 1980.

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    Zhang, Y.; Wang, J.; Liu, J.; Han, J.; Xiong, S.; Yong, W.; Zhao, Z. Combination of ESI and MALDI mass spectrometry for qualitative, semi-quantitative and in situ analysis of gangliosides in brain. Sci. Rep. 2016, 6, 25289,  DOI: 10.1038/srep25289

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    Combination of ESI and MALDI mass spectrometry for qualitative, semi-quantitative and in situ analysis of gangliosides in brain

    Zhang, Yangyang; Wang, Jun; Liu, Jian'an; Han, Juanjuan; Xiong, Shaoxiang; Yong, Weidong; Zhao, Zhenwen

    Scientific Reports (2016), 6 (), 25289CODEN: SRCEC3; ISSN:2045-2322. (Nature Publishing Group)

    Gangliosides are a family of complex lipids that are abundant in the brain. There is no doubt the investigations about the distribution of gangliosides in brian and the relationship between gangliosides and Alzheimer's disease is profound. However, these investigations are full of challenges due to the structural complexity of gangliosides. In this work, the method for efficient extn. and enrichment of gangliosides from brain was established. Moreover, the distribution of gangliosides in brain was obtained by matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI). It was found that 3-aminoquinoline (3-AQ) as matrix was well-suited for MALDI MS anal. of gangliosides in neg. ion mode. In addn., the pretreatment by ethanol (EtOH) cleaning brain section and the addn. of ammonium formate greatly improved the MS signal of gangliosides in the brain section when MALDI MSI anal. was employed. The distribution of ganliosides in cerebral cortex, hippocampus and cerebellum was resp. acquired by electrospray ionization (ESI) MS and MALDI MSI, and the data were compared for reliability evaluation of MALDI MSI. Further, applying MALDI MSI technol., the distribution of gangliosides in amyloid precursor protein transgenic mouse brain was obtained, which may provide a new insight for bioresearch of Alzheimer's disease (AD).
49. 49

    Colsch, B.; Jackson, S. N.; Dutta, S.; Woods, A. S. Molecular Microscopy of Brain Gangliosides: Illustrating their Distribution in Hippocampal Cell Layers. ACS Chem. Neurosci. 2011, 2, 213– 222,  DOI: 10.1021/cn100096h

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    Molecular Microscopy of Brain Gangliosides: Illustrating their Distribution in Hippocampal Cell Layers

    Colsch, Benoit; Jackson, Shelley N.; Dutta, Sucharita; Woods, Amina S.

    ACS Chemical Neuroscience (2011), 2 (4), 213-222CODEN: ACNCDM; ISSN:1948-7193. (American Chemical Society)

    Gangliosides are amphiphilic mols. found in the outer layer of plasma membranes of all vertebrate cells. They play a major role in cell recognition and signaling and are involved in diseases affecting the central nervous system (CNS). We are reporting the differential distribution of ganglioside species in the rat brain's cerebrum, based on their ceramide assocd. core, and for the first time the presence of acetylation detected by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, which was used to map and image gangliosides with detailed structural information and histol. accuracy. In the hippocampus, localization of the major species GM1, GD1, O-acetylGD1, GT1, and O-acetylGT1 depends on the sphingoid base (d18:1 sphingosine or d20:1 eicosasphingosine) in the mol. layer of the dentate gyrus (ML), which is made up of three distinct layers, the inner mol. layer (IML), which contains sphingosine exclusively, and the middle mol. layer (MML) and the outer mol. layer (OML) where eicosasphingosine is the only sphingoid base. These results demonstrate that there is a different distribution of gangliosides in neuronal axons and dendrites depending on the ceramide core of each layer. GM3, GM2, GD3, and GD2 contain sphingosine predominantly and are mainly present in body cell layers, which are made up of the pyramidal cell layer (Py) and the granular layer of the dentate gyrus (GL), in contrast with GQ1 and the O-acetylated forms of GD1, GT1, and GQ1 gangliosides, which contain both sphingoid bases. However their distribution is based on the sialylated and acetylated oligosaccharide chains in the neuronal cell bodies.