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Sample records for 9-o-acetyl gd3 gangliosides

  1. Ganglioside 9-O-acetyl GD3 expression is upregulated in the regenerating peripheral nerve.

    PubMed

    Ribeiro-Resende, V T; Oliveira-Silva, A; Ouverney-Brandão, S; Santiago, M F; Hedin-Pereira, C; Mendez-Otero, R

    2007-06-15

    Evidence accumulates suggesting that 9-O-acetylated gangliosides, recognized by a specific monoclonal antibody (Jones monoclonal antibody), are involved in neuronal migration and axonal growth. These molecules are expressed in rodent embryos during the period of axon extension of peripheral nerves and are absent in adulthood. We therefore aimed at verifying if these molecules are re-expressed in adult rats during peripheral nerve regeneration. In this work we studied the time course of ganglioside 9-O-acetyl GD3 expression during regeneration of the crushed sciatic nerve and correlated this expression with the time course of axonal regeneration as visualized by immunohistochemistry for neurofilament 200 in the nerve. We have found that the ganglioside 9-O-acetyl GD3 is re-expressed during the period of regeneration and this expression correlates spatio-temporally with the arrival of axons to the lesion site. Confocal analysis of double and triple labeling experiments allowed the localization of this ganglioside to Schwann cells encircling growing axons in the sciatic nerve. Explant cultures of peripheral nerves also revealed ganglioside expressing reactive Schwann cells migrating from the normal and previously crushed nerve. Ganglioside 9-O-acetyl GD3 is also upregulated in DRG neurons and motoneurons of the ventral horn of spinal cord showing that the reexpression of this molecule is not restricted to Schwann cells. These results suggest that ganglioside 9-O-acetyl GD3 may be involved in the regrowth of sciatic nerve axons after crush being upregulated in both neurons and glia.

  2. Involvement of 9-O-Acetyl GD3 ganglioside in Mycobacterium leprae infection of Schwann cells.

    PubMed

    Ribeiro-Resende, Victor Túlio; Ribeiro-Guimarães, Michelle Lopes; Lemes, Robertha Mariana Rodrigues; Nascimento, Isis Cristina; Alves, Lucinéia; Mendez-Otero, Rosalia; Pessolani, Maria Cristina Vidal; Lara, Flávio Alves

    2010-10-29

    Mycobacterium leprae (ML), the etiologic agent of leprosy, mainly affects the skin and peripheral nerves, leading to demyelization and loss of axonal conductance. Schwann cells (SCs) are the main cell population infected by ML in the nerves, and infection triggers changes in the SC phenotype from a myelinated to a nonmyelinated state. In the present study, we show that expression of 9-O-acetyl GD3, a ganglioside involved in cellular anti-apoptotic signaling and nerve regeneration, increases in SCs following infection with ML. Observation by confocal microscopy together with coimmunoprecipitation suggested that this ganglioside participates in ML attachment and internalization by SC. Immunoblockage of 9-O-acetyl GD3 in vitro significantly reduced adhesion of ML to SC surfaces. Finally, we show that activation of the MAPK (ERK 1/2) pathway and SC proliferation, two known effects of ML on SCs that result in demyelization, are significantly reduced when the 9-O-acetyl GD3 ganglioside is immunoblocked. Taken together, these data suggest the involvement of 9-O-acetyl GD3 in ML infection on SCs.

  3. Expression of ganglioside 9-O acetyl GD3 in undifferentiated embryonic stem cells.

    PubMed

    Azevedo-Pereira, Ricardo Luiz; Morrot, Alexandre; Machado, Gabriele Santos; Paredes, Bruno Diaz; Rodrigues, Deivid de Carvalho; de Carvalho, Antonio Carlos Campos; Mendez-Otero, Rosalia

    2015-01-01

    Embryonic stem cells (ES cells) express a transient and heterogeneous pattern of molecules, which suggests a notable mechanism to control self-renewal avoid the differentiation into germ layers. We show that 9-O-acetyl GD3 (9OacGD3), a highly expressed b-series ganglioside in neural stem (NS) cells, is expressed in undifferentiated mouse ES cells in a heterogeneous fashion. After sorting, undifferentiated 9OacGD3(+) ES cell population had higher levels of nestin and Sox2 mRNA than the 9OacGD3(-) cells. Even with elevated expression of these neural transcription factors, 9OacGD3(+) cells did not give rise to more neural progenitors than 9OacGD3(-) cells. Expression of 9OacGD3 was recovered from 9OacGD3(-) cell population, demonstrating that expression of this ganglioside in mouse embryonic stem cells is transient, and does not reflect cell fate. Our findings show that the ganglioside 9OacGD3 is expressed heterogeneously and transiently in ES cells, and this expression corresponds to higher levels of Sox2 and Nestin transcripts. © 2014 International Federation for Cell Biology.

  4. Neuroblast migration and P2Y(1) receptor mediated calcium signalling depend on 9-O-acetyl GD3 ganglioside.

    PubMed

    Santiago, Marcelo F; Scemes, Eliana

    2012-09-11

    Previous studies indicated that a ganglioside 9acGD3 (9-O-acetyl GD3) antibody [the J-Ab (Jones antibody)] reduces GCP (granule cell progenitor) migration in vitro and in vivo. We here investigated, using cerebellar explants of post-natal day (P) 6 mice, the mechanism by which 9acGD3 reduces GCP migration. We found that immunoblockade of the ganglioside with the J-Ab or the lack of GD3 synthase reduced GCP in vitro migration and the frequency of Ca(2+) oscillations. Immunocytochemistry and pharmacological assays indicated that GCPs expressed P2Y(1)Rs (P2Y(1) receptors) and that deletion or blockade of these receptors decreased the migration rate of GCPs and the frequency of Ca(2+) oscillations. The reduction in P2Y(1)-mediated calcium signals seen in Jones-treated and GD3 synthase-null GCPs were paralleled by P2Y(1)R internalization. We conclude that 9acGD3 controls GCP migration by influencing P2Y(1)R cellular distribution and function.

  5. Role of the 9-O-acetyl GD3 in subventricular zone neuroblast migration.

    PubMed

    Miyakoshi, L M; Todeschini, A R; Mendez-Otero, R; Hedin-Pereira, C

    2012-02-01

    In the mammalian central nervous system the subventricular zone (SVZ) is one of the few neurogenic regions that persist postnatally. Neuroblasts generated in the SVZ migrate from this region tangentially towards the olfactory bulbs via the rostral migratory stream (RMS) and give rise to interneurons. In previous studies, an important role in radial migration of cerebellar granule neurons has been attributed to the 9-O-acetylated GD3 ganglioside. Previous data demonstrated the expression of 9-O-acetyl GD3 in the rostral migratory stream in vivo as well as in chains of neuroblasts that migrate from SVZ explants in vitro. Herein, using the Jones monoclonal antibody (Jones mAb), we combined SVZ explant migration measurements and time-lapse videomicroscopy of migrating neuroblasts to show that SVZ neuroblast migration is inhibited by the antibody that recognizes 9-O-acetyl GD3 but not by A2B5, an antibody that recognizes c-series gangliosides. In addition, inhibition of ganglioside synthesis results in reduction of migratory halos around SVZ explants. Coherently, we show that most migratory neuroblasts which express the embryonic form of NCAM co-express 9acGD3. Also, we observe that some of the ganglioside positive neuroblasts also express nestin consistent with their maintained proliferative capacity. These results strongly support that the 9-O-acetyl GD3 has a pivotal role in neuroblast migration from SVZ, being fundamental for cell-cell and cell-substrate interactions in this region. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Purification and structural characterization of de-N-acetylated form of GD3 ganglioside present in human melanoma tumors.

    PubMed

    Popa, Iuliana; Pons, Alexandre; Mariller, Christophe; Tai, Tadashi; Zanetta, Jean-Pierre; Thomas, Luc; Portoukalian, Jacques

    2007-04-01

    The presence of gangliosides containing de-N-acetylated sialic acids in human tissues has been so far shown by using mouse monoclonal antibodies specific for the de-N-acetylated forms, but the isolation and chemical characterization of such compounds have not yet been performed. Since indirect evidence suggested that de-N-acetylGD3 ganglioside could be present in human melanoma tumors, we analyzed the gangliosides purified from a 500-g pool of those tumors. The de-N-acetylGD3 that was found to migrate just below GD2 in thin-layer chromatography was isolated from the disialogangliosides by high-pressure liquid chromatography using the specific antibody SGR37 to monitor the elution. The amount of antigen was found to be 320 ng per gram of fresh tumor or 0.1% of total gangliosides. Gas chromatography-mass spectrometry analysis of the antibody-positive ganglioside showed that sialic acids were formed of one molecule of N-acetylneuraminic acid and one molecule of neuraminic acid. Radioactive re-N-acetylation of the antigen yielded a GD3-like ganglioside with the radioactive label on the external sialic acid. The constitutive fatty acids were found to differ markedly from those of GD3 and 9-O-acetylGD3 isolated from the same pool of tumors. The major fatty acids were C16:0 and C18:0 in de-N-acetylGD3, whereas GD3 and its 9-O-acetylated derivative contained a large amount of C24:1. These data show that de-N-acetylGD3 ganglioside is indeed present in human melanoma tumors, and the fatty acid content suggests the existence of a de-N-acetylase mostly active on the molecular species of gangliosides with short-chain fatty acids.

  7. Uptake and fate of ganglioside GD3 in human intestinal Caco-2 cells.

    PubMed

    Schnabl, Kareena L; Larcelet, Marjorie; Thomson, Alan B R; Clandinin, Michael T

    2009-07-01

    Ganglioside GD3 is a glycosphingolipid found in colostrum, developing tissues, and tumors and is known to regulate cell growth, differentiation, apoptosis, and inflammation. Feeding a GD3-enriched diet to rats increases GD3 in intestinal lipid rafts and blood. The mechanism, efficiency, and fate of ganglioside absorption by human enterocytes have not been investigated. A model to study GD3 uptake by human intestinal cells was developed to test the hypothesis that enterocyte GD3 uptake is time and concentration dependent, with uptake efficiency and fate influenced by route of delivery. Caco-2 cells were exposed to GD3 on the apical or basolateral membrane (BLM) side for 6, 24, and 48 h. GD3 uptake, retention, transfer, and metabolism was determined. GD3 uptake across the apical and BLM was time and concentration dependent and reached a plateau. GD3 uptake across the BLM was more efficient than apical delivery. Apical GD3 was metabolized with some cell retention and transfer, whereas basolateral GD3 was mostly metabolized. This study demonstrates efficient GD3 uptake by enterocytes and suggests that the route of delivery influences ganglioside uptake and fate.

  8. Enhancement of malignant properties of human osteosarcoma cells with disialyl gangliosides GD2/GD3.

    PubMed

    Shibuya, Hidenobu; Hamamura, Kazunori; Hotta, Hiroshi; Matsumoto, Yasuyuki; Nishida, Yoshihiro; Hattori, Hisashi; Furukawa, Keiko; Ueda, Minoru; Furukawa, Koichi

    2012-09-01

    The expression and implications of gangliosides in human osteosarcomas have not been systematically analyzed. In this study, we showed that gangliosides GD3 and GD2 are highly expressed in the majority of human osteosarcoma cell lines derived from oral cavity regions. Introduction of GD3 synthase cDNA into a GD3/GD2-negative (GD3/GD2-) human osteosarcoma subline resulted in the establishment of GD3/GD2+ transfectant cells. They showed increased cell migration and invasion activities in wound healing and Boyden chamber invasion assays, respectively, compared to the control cells. When treated with serum, GD3/GD2+ cells showed stronger tyrosine phosphorylation of p130Cas, focal adhesion kinase, and paxillin than GD3/GD2- cells. In particular, paxillin underwent much stronger phosphorylation, suggesting its role in cell motility. Furthermore, we tried to dissect the roles of GD3 and GD2 in the malignant properties of the transfectant cells by establishing single ganglioside-expressing cells, that is, either GD3 or GD2. Although GD3/GD2+ cells showed the most malignant properties, GD2+ cells showed almost equivalent levels to GD3/GD2+ cells in invasion and migration activities, and in the intensities of tyrosine phosphorylation of paxillin. Among Src family kinases, Lyn was expressed predominantly, and was involved in the invasion and motility of GD3- and/or GD2-expressing transfectants. Furthermore, it was elucidated by gene silencing that Lyn was located in a different pathway from that of FAK to eventually lead paxillin activation. These results suggested that GD2/GD3 are responsible for the enhancement of the malignant features of osteosarcomas, and might be candidate targets in molecular-targeted therapy. © 2012 Japanese Cancer Association.

  9. Detection of GD3 ganglioside in primary melanomas depends on histopathologic procedures used for tumor preservation.

    PubMed

    Debarbieux, Sébastien; Popa, Iuliana; Thomas, Luc; Kanitakis, Jean; Pirot, Fabrice; Portoukalian, Jacques; Haftek, Marek

    2009-01-01

    Gangliosides, cell surface glycosphingolipids, are implicated in diverse biologic functions potentially important for tumor growth. Because expression of the GD3 ganglioside may have an impact on the melanoma malignancy, and therefore on the patient prognosis, we evaluated the feasibility of a retrospective immunohistochemical study of GD3 in paraffin embedded biopsies of primary melanomas. Immunoperoxidase staining of frozen and deparaffinized sections of melanoma lesions with two anti-GD3 antibodies was compared using Dako biotin-streptavidin detection kit. Residual ganglioside content was evaluated in the tissues submitted to routine histopathologic procedures using HPLC. A strong and reproducible staining was obtained with both antibodies on frozen sections of all 17 melanoma samples. However, only KM641 antibody could detect GD3 on deparaffinized sections. Biochemical quantification revealed that the Bouin fixative resulted in degradation of GD3. Additionally, most of GD3 was eluted from the tissue samples during dehydration and re-hydration steps. A subgroup of tumors particularly rich in GD3 could be detected on deparaffinized sections after standard formaldehyde fixation. Clinical evolution of such melanomas can now be compared to the group with low GD3 expression. However, any Bouin-fixed, paraffin-embedded biopsies should be excluded from such a retrospective study.

  10. Expression of GD2 and GD3 gangliosides in human embryonic neural stem cells.

    PubMed

    Yanagisawa, Makoto; Yoshimura, Saori; Yu, Robert K

    2011-04-07

    NSCs (neural stem cells) are undifferentiated neural cells endowed with a high potential for proliferation and a capacity for self-renewal with retention of multipotency to differentiate into neurons and glial cells. It has been recently reported that GD3, a b-series ganglioside, is a marker molecule for identifying and isolating mouse NSCs. However, the expression of gangliosides in human NSCs is largely unknown. In the present study, we analysed the expression of gangliosides, GD2 and GD3, in human NSCs that were isolated from human brains at gestational week 17 in the form of neurospheres, which are floating clonal aggregates formed by NSCs in vitro. Employing immunocytochemistry, we found that human NSCs were strongly reactive to anti-GD2 antibody and relatively weakly reactive to anti-GD3 antibody. Treatment of these cells with an organic solvent such as 100% methanol, which selectively removes glycolipids from plasma membrane, abolished the immunoreactivity with those antibodies, indicating that the reactivity was due to GD2 and GD3, but not to GD2-/GD3-like glycoproteins or proteoglycans. The immunoreactivity of human NSCs to antibody against SSEA-1 (stage-specific embryonic antigen-1), a well-known carbohydrate antigen of NSCs, was not decreased by the treatment with 100% methanol, indicating that SSEA-1 is mainly carried by glycoproteins and/or proteoglycans in human NSCs. Our study suggests that GD2 and GD3 can be marker gangliosides for identifying human NSCs.

  11. Characterization of GD3 ganglioside as a novel biomarker of mouse neural stem cells.

    PubMed

    Nakatani, Yoshihiko; Yanagisawa, Makoto; Suzuki, Yusuke; Yu, Robert K

    2010-01-01

    Neural stem cells (NSCs) are undifferentiated neural cells characterized by their high proliferative potential and the capacity for self-renewal with retention of multipotency. Over the past two decades, there has been a huge effort to identify NSCs morphologically, genetically, and molecular biologically. It is still controversial, however, what bona fide NSCs are. To define and characterize NSCs more systematically, it is crucial to explore novel cell-surface marker molecules of NSCs. In this study, we focused on GD3, a b-series ganglioside that is enriched in the immature brain and the subventricular zone (SVZ) of the postnatal and adult brain, and evaluated the usefulness of GD3 as a cell-surface biomarker for identifying NSCs. We demonstrated that GD3 was expressed in more than 80% of NSCs prepared from embryonic, postnatal, and adult mouse brain tissue by the neurosphere culture method. The percentage of GD3-expressing NSCs in neurospheres was nearly the same as it was in neurospheres derived from embryonic, postnatal, and adult brains but decreased drastically to about 40% after differentiation. GD3(+) cells isolated from embryonic mouse striata, postnatal, and adult mouse SVZs by fluorescence-activated cell sorting with an R24 anti-GD3 monoclonal antibody efficiently generated neurospheres compared with GD3(-) cells. These cells possessed multipotency to differentiate into neurons, astrocytes, and oligodendrocytes. These data indicate that GD3 is a unique and powerful cell-surface biomarker to identify and isolate NSCs.

  12. Longitudinal evolution of the concentration of gangliosides GM3 and GD3 in human milk.

    PubMed

    Giuffrida, Francesca; Elmelegy, Isabelle Masserey; Thakkar, Sagar K; Marmet, Cynthia; Destaillats, Frédéric

    2014-10-01

    It has been reported that dietary gangliosides may have an important role in preventing infections and in brain development during early infancy. However, data related to the evolution of their concentration over the different stages of lactation are scarce. Liquid chromatography coupled with electrospray ionization high resolution mass spectrometer (LC/ESI-HR-MS) has been optimized to quantify the two major ganglioside classes, i.e., aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDGlcp(1-1)Cer (GD3) and aNeu5Ac(2-3)bDGalp(1-4)bDGlcp(1-1)Cer (GM3) in human milk. Gangliosides were extracted using chloroform and methanol, further purified by solid-phase extraction and separated by reversed-phase liquid chromatography. Repeatability, intermediate reproducibility, and recovery values were assessed to validate the method. In human milk, GD3 and GM3 could be quantified at the level of 0.1 and 0.2 μg/mL, respectively, with relative standard deviation of repeatability [CV(r)] and intermediate reproducibility [CV(iR)] values ranging from 1.9 to 15.0 % and 1.9 to 22.5 %, respectively. The described method was used to quantify GD3 and GM3 in human milk samples collected from 450 volunteers between 0 and 11 days and at 30, 60 and 120 days postpartum, providing for the first time the concentration of these minor lipids in a large cohort. The content of total gangliosides ranged from 8.1 and 10.7 μg/mL and the mean intake of gangliosides in infants 30, 60 and 120 days postpartum could be estimated at about 5.5, 7.0 and 8.6 mg of total gangliosides per day, respectively, when infants were exclusively breastfed.

  13. Evidence for the involvement of GD3 ganglioside in autophagosome formation and maturation

    PubMed Central

    Matarrese, Paola; Garofalo, Tina; Manganelli, Valeria; Gambardella, Lucrezia; Marconi, Matteo; Grasso, Maria; Tinari, Antonella; Misasi, Roberta; Malorni, Walter; Sorice, Maurizio

    2014-01-01

    Sphingolipids are structural lipid components of cell membranes, including membrane of organelles, such as mitochondria or endoplasmic reticulum, playing a role in signal transduction as well as in the transport and intermixing of cell membranes. Sphingolipid microdomains, also called lipid rafts, participate in several metabolic and catabolic cell processes, including apoptosis. However, the defined role of lipid rafts in the autophagic flux is still unknown. In the present study we analyzed the role of gangliosides, a class of sphingolipids, in autolysosome morphogenesis in human and murine primary fibroblasts by means of biochemical and analytical cytology methods. Upon induction of autophagy, by using amino acid deprivation as well as tunicamycin, we found that GD3 ganglioside, considered as a paradigmatic raft constituent, actively contributed to the biogenesis and maturation of autophagic vacuoles. In particular, fluorescence resonance energy transfer (FRET) and coimmunoprecipitation analyses revealed that this ganglioside interacts with phosphatidylinositol 3-phosphate and can be detected in immature autophagosomes in association with LC3-II as well as in autolysosomes associated with LAMP1. Hence, it appears as a structural component of autophagic flux. Accordingly, we found that autophagy was significantly impaired by knocking down ST8SIA1/GD3 synthase (ST8 α-N-acetyl-neuraminide α-2,8-sialyltransferase 1) or by altering sphingolipid metabolism with fumonisin B1. Interestingly, exogenous administration of GD3 ganglioside was capable of reactivating the autophagic process inhibited by fumonisin B1. Altogether, these results suggest that gangliosides, via their molecular interaction with autophagy-associated molecules, could be recruited to autophagosome and contribute to morphogenic remodeling, e.g., to changes of membrane curvature and fluidity, finally leading to mature autolysosome formation. PMID:24589479

  14. Evidence for the involvement of GD3 ganglioside in autophagosome formation and maturation.

    PubMed

    Matarrese, Paola; Garofalo, Tina; Manganelli, Valeria; Gambardella, Lucrezia; Marconi, Matteo; Grasso, Maria; Tinari, Antonella; Misasi, Roberta; Malorni, Walter; Sorice, Maurizio

    2014-05-01

    Sphingolipids are structural lipid components of cell membranes, including membrane of organelles, such as mitochondria or endoplasmic reticulum, playing a role in signal transduction as well as in the transport and intermixing of cell membranes. Sphingolipid microdomains, also called lipid rafts, participate in several metabolic and catabolic cell processes, including apoptosis. However, the defined role of lipid rafts in the autophagic flux is still unknown. In the present study we analyzed the role of gangliosides, a class of sphingolipids, in autolysosome morphogenesis in human and murine primary fibroblasts by means of biochemical and analytical cytology methods. Upon induction of autophagy, by using amino acid deprivation as well as tunicamycin, we found that GD3 ganglioside, considered as a paradigmatic raft constituent, actively contributed to the biogenesis and maturation of autophagic vacuoles. In particular, fluorescence resonance energy transfer (FRET) and coimmunoprecipitation analyses revealed that this ganglioside interacts with phosphatidylinositol 3-phosphate and can be detected in immature autophagosomes in association with LC3-II as well as in autolysosomes associated with LAMP1. Hence, it appears as a structural component of autophagic flux. Accordingly, we found that autophagy was significantly impaired by knocking down ST8SIA1/GD3 synthase (ST8 α-N-acetyl-neuraminide α-2,8-sialyltransferase 1) or by altering sphingolipid metabolism with fumonisin B1. Interestingly, exogenous administration of GD3 ganglioside was capable of reactivating the autophagic process inhibited by fumonisin B1. Altogether, these results suggest that gangliosides, via their molecular interaction with autophagy-associated molecules, could be recruited to autophagosome and contribute to morphogenic remodeling, e.g., to changes of membrane curvature and fluidity, finally leading to mature autolysosome formation.

  15. Mice lacking GD3 synthase display morphological abnormalities in the sciatic nerve and neuronal disturbances during peripheral nerve regeneration.

    PubMed

    Ribeiro-Resende, Victor Túlio; Araújo Gomes, Tiago; de Lima, Silmara; Nascimento-Lima, Maiara; Bargas-Rega, Michele; Santiago, Marcelo Felipe; Reis, Ricardo Augusto de Melo; de Mello, Fernando Garcia

    2014-01-01

    The ganglioside 9-O-acetyl GD3 is overexpressed in peripheral nerves after lesioning, and its expression is correlated with axonal degeneration and regeneration in adult rodents. However, the biological roles of this ganglioside during the regenerative process are unclear. We used mice lacking GD3 synthase (Siat3a KO), an enzyme that converts GM3 to GD3, which can be further converted to 9-O-acetyl GD3. Morphological analyses of longitudinal and transverse sections of the sciatic nerve revealed significant differences in the transverse area and nerve thickness. The number of axons and the levels of myelin basic protein were significantly reduced in adult KO mice compared to wild-type (WT) mice. The G-ratio was increased in KO mice compared to WT mice based on quantification of thin transverse sections stained with toluidine blue. We found that neurite outgrowth was significantly reduced in the absence of GD3. However, addition of exogenous GD3 led to neurite growth after 3 days, similar to that in WT mice. To evaluate fiber regeneration after nerve lesioning, we compared the regenerated distance from the lesion site and found that this distance was one-fourth the length in KO mice compared to WT mice. KO mice in which GD3 was administered showed markedly improved regeneration compared to the control KO mice. In summary, we suggest that 9-O-acetyl GD3 plays biological roles in neuron-glia interactions, facilitating axonal growth and myelination induced by Schwann cells. Moreover, exogenous GD3 can be converted to 9-O-acetyl GD3 in mice lacking GD3 synthase, improving regeneration.

  16. Mice Lacking GD3 Synthase Display Morphological Abnormalities in the Sciatic Nerve and Neuronal Disturbances during Peripheral Nerve Regeneration

    PubMed Central

    Ribeiro-Resende, Victor Túlio; Gomes, Tiago Araújo; de Lima, Silmara; Nascimento-Lima, Maiara; Bargas-Rega, Michele; Santiago, Marcelo Felipe; Reis, Ricardo Augusto de Melo; de Mello, Fernando Garcia

    2014-01-01

    The ganglioside 9-O-acetyl GD3 is overexpressed in peripheral nerves after lesioning, and its expression is correlated with axonal degeneration and regeneration in adult rodents. However, the biological roles of this ganglioside during the regenerative process are unclear. We used mice lacking GD3 synthase (Siat3a KO), an enzyme that converts GM3 to GD3, which can be further converted to 9-O-acetyl GD3. Morphological analyses of longitudinal and transverse sections of the sciatic nerve revealed significant differences in the transverse area and nerve thickness. The number of axons and the levels of myelin basic protein were significantly reduced in adult KO mice compared to wild-type (WT) mice. The G-ratio was increased in KO mice compared to WT mice based on quantification of thin transverse sections stained with toluidine blue. We found that neurite outgrowth was significantly reduced in the absence of GD3. However, addition of exogenous GD3 led to neurite growth after 3 days, similar to that in WT mice. To evaluate fiber regeneration after nerve lesioning, we compared the regenerated distance from the lesion site and found that this distance was one-fourth the length in KO mice compared to WT mice. KO mice in which GD3 was administered showed markedly improved regeneration compared to the control KO mice. In summary, we suggest that 9-O-acetyl GD3 plays biological roles in neuron-glia interactions, facilitating axonal growth and myelination induced by Schwann cells. Moreover, exogenous GD3 can be converted to 9-O-acetyl GD3 in mice lacking GD3 synthase, improving regeneration. PMID:25330147

  17. Ganglioside GD3 induces convergence and synergism of adhesion and hepatocyte growth factor/Met signals in melanomas.

    PubMed

    Furukawa, Keiko; Kambe, Mariko; Miyata, Maiko; Ohkawa, Yuki; Tajima, Orie; Furukawa, Koichi

    2014-01-01

    Ganglioside GD3 is highly expressed in human melanomas and enhances malignant properties of melanomas, such as cell proliferation and invasion activity. In this study, we analyzed the effects of GD3 expression on cell signals triggered by hepatocyte growth factor (HGF)/Met interaction and by adhesion to collagen type I (CL-I). Although stimulation of melanoma N1 cells (GD3+ and GD3-) with either HGF or adhesion to CL-I did not show marked differences in the phosphorylation levels of Akt at Ser473 and Thr308 between two types of cells, simultaneous treatment resulted in definite and markedly increased activation of Akt in GD3+ cells. Similar increases were also shown in Erk1/2 phosphorylation levels with the costimulation in GD3+ cells. When resistance to induced apoptosis by H2O2 was examined, only GD3+ cells treated with both HGF and adhesion to CL-I showed clearly low percentages of dead cells compared with GD3- cells or GD3+ cells treated with either one of the stimulants. Cell growth measured by 5-ethynyl-2' deoxyuridine uptake also showed synergistic effects in GD3+ cells. These results suggested that GD3 plays a crucial role in the convergence of multiple signals, leading to the synergistic effects of those signals on malignant properties of melanomas. © 2013 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  18. Ganglioside GD3 induces convergence and synergism of adhesion and hepatocyte growth factor/Met signals in melanomas

    PubMed Central

    Furukawa, Keiko; Kambe, Mariko; Miyata, Maiko; Ohkawa, Yuki; Tajima, Orie; Furukawa, Koichi

    2014-01-01

    Ganglioside GD3 is highly expressed in human melanomas and enhances malignant properties of melanomas, such as cell proliferation and invasion activity. In this study, we analyzed the effects of GD3 expression on cell signals triggered by hepatocyte growth factor (HGF)/Met interaction and by adhesion to collagen type I (CL-I). Although stimulation of melanoma N1 cells (GD3+ and GD3−) with either HGF or adhesion to CL-I did not show marked differences in the phosphorylation levels of Akt at Ser473 and Thr308 between two types of cells, simultaneous treatment resulted in definite and markedly increased activation of Akt in GD3+ cells. Similar increases were also shown in Erk1/2 phosphorylation levels with the costimulation in GD3+ cells. When resistance to induced apoptosis by H2O2 was examined, only GD3+ cells treated with both HGF and adhesion to CL-I showed clearly low percentages of dead cells compared with GD3− cells or GD3+ cells treated with either one of the stimulants. Cell growth measured by 5-ethynyl-2‘ deoxyuridine uptake also showed synergistic effects in GD3+ cells. These results suggested that GD3 plays a crucial role in the convergence of multiple signals, leading to the synergistic effects of those signals on malignant properties of melanomas. PMID:24372645

  19. Ganglioside GD3 monoclonal antibody-induced paxillin tyrosine phosphorylation and filamentous actin assembly in cerebellar growth cones.

    PubMed

    Yuyama, Kohei; Sekino-Suzuki, Naoko; Yamamoto, Naomasa; Kasahara, Kohji

    2011-03-01

    We have demonstrated that antibody to ganglioside GD3 (R24) immunoprecipitates src-family tyrosine kinase Lyn from primary cerebellar granule cells and R24 treatment of the intact cells induces Lyn activation and rapid tyrosine phosphorylation of several substrates, suggesting the functional association of ganglioside GD3 with Lyn. In this study, R24 treatment of primary cerebellar granule cells enhances phosphorylation of paxillin at tyrosine residue 118 and induces filamentous actin assembly and neurite outgrowth. R24 treatment of cerebellar growth cone membrane fraction induces prominent tyrosine phosphorylation of 68 kDa protein which comigrates with phosphopaxillin at tyrosine residue 118. Tyrosine phosphorylation of paxillin is known to regulate actin cytoskeleton-dependent changes in cell morphology. Signal transduction by ganglioside GD3 is involved in growth cone morphology via tyrosine phosphorylation of paxillin. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  20. GD3, an overexpressed tumor-derived ganglioside, mediates the apoptosis of activated but not resting T cells.

    PubMed

    Sa, Gaurisankar; Das, Tanya; Moon, Christina; Hilston, Cynthia M; Rayman, Patricia A; Rini, Brian I; Tannenbaum, Charles S; Finke, James H

    2009-04-01

    We previously elucidated an important role for gangliosides in renal cell carcinoma-mediated T lymphocyte apoptosis, although the mechanism by which they mediated lymphocyte death remained unclear. Here, we show that when added in purified form, GD3 is internalized by activated T cells, initiating a series of proapoptotic events, including the induction of reactive oxygen species (ROS), an enhancement of p53 and Bax accumulation, an increase in mitochondrial permeability, cytochrome c release, and the activation of caspase-9. GD3-induced apoptosis of activated T cells was dose dependent and inhibitable by pretreating the lymphocytes with N-acetylcysteine, cyclosporin A, or bongkrekic acid, emphasizing the essential role of ROS and mitochondrial permeability to the process. Ganglioside-induced T-cell killing was associated with the caspase-dependent degradation of nuclear factor-kappaB-inducible, antiapoptotic proteins, including RelA; this suggests that their loss is initiated only after the cascade is activated and that their disappearance amplifies but not triggers GD3 susceptibility. Resting T cells did not internalize appreciable levels of GD3 and did not undergo any of the proapoptotic changes that characterize activated T lymphocytes exposed to the ganglioside. RelA overexpression endows Jurkat cells with resistance to GD3-mediated apoptosis, verifying the role of the intact transcription factor in mediating protection from the ganglioside.

  1. Altered ganglioside GD3 in HeLa cells might influence the cytotoxic abilities of NK cells.

    PubMed

    Lee, Wen-Chi; Lee, Wen-Ling; Shyong, Wen-Yuann; Yang, Lin-Wei; Ko, Min-Chun; Yeh, Chang-Ching; Hsieh, Shie-Liang Edmond; Wang, Peng-Hui

    2012-06-01

    Previously, we found that altered sialidases in HeLa cells in a natural killer-HeLa (NK-HeLa) coculture system contributed to the decreased cytotoxic ability of NK cells. However, changes that occur in the glycosylation of the HeLa cells in the NK-HeLa coculture system remain unknown. An NK-HeLa coculture system was used to examine the changes that occur in the gangliosides of HeLa cells. GD3 expression in HeLa cells was significantly increased in the NK-HeLa coculture system. Exogenous ganglioside GD3 decreased the cytotoxic ability of the NK cells, which could be restored by the addition of the anti-GD3 antibody. Coadministration of GD3 and sialidase further decreased the cytotoxic ability of the NK cells, which could be partially restored by the addition of a sialidase inhibitor (DANA). GD3 expression in HeLa cells also decreased following DANA treatment. This study suggests that interactions between ganglioside GD3 and sialidases in HeLa cells influence the cytotoxic ability of NK cells. Copyright © 2012. Published by Elsevier B.V.

  2. Targeted Delivery of Immunotoxin by Antibody to Ganglioside GD3: A Novel Drug Delivery Route for Tumor Cells

    PubMed Central

    Torres Demichelis, Vanina; Vilcaes, Aldo A.; Iglesias-Bartolomé, Ramiro; Ruggiero, Fernando M.; Daniotti, Jose L.

    2013-01-01

    Gangliosides are sialic acid-containing glycolipids expressed on plasma membranes from nearly all vertebrate cells. The expression of ganglioside GD3, which plays essential roles in normal brain development, decreases in adults but is up regulated in neuroectodermal and epithelial derived cancers. R24 antibody, directed against ganglioside GD3, is a validated tumor target which is specifically endocytosed and accumulated in endosomes. Here, we exploit the internalization feature of the R24 antibody for the selective delivery of saporin, a ribosome-inactivating protein, to GD3-expressing cells [human (SK-Mel-28) and mouse (B16) melanoma cells and Chinese hamster ovary (CHO)-K1 cells]. This immunotoxin showed a specific cytotoxicity on tumor cells grew on 2D monolayers, which was further evident by the lack of any effect on GD3-negative cells. To estimate the potential antitumor activity of R24-saporin complex, we also evaluated the effect of the immunotoxin on the clonogenic growth of SK-Mel-28 and CHO-K1GD3+ cells cultured in attachment-free conditions. A drastic growth inhibition (>80–90%) of the cell colonies was reached after 3 days of immunotoxin treatment. By the contrary, colonies continue to growth at the same concentration of the immuntoxin, but in the absence of R24 antibody, or in the absence of both immunotoxin and R24, undoubtedly indicating the specificity of the effect observed. Thus, the ganglioside GD3 emerge as a novel and attractive class of cell surface molecule for targeted delivery of cytotoxic agents and, therefore, provides a rationale for future therapeutic intervention in cancer. PMID:23383146

  3. Targeted delivery of immunotoxin by antibody to ganglioside GD3: a novel drug delivery route for tumor cells.

    PubMed

    Torres Demichelis, Vanina; Vilcaes, Aldo A; Iglesias-Bartolomé, Ramiro; Ruggiero, Fernando M; Daniotti, Jose L

    2013-01-01

    Gangliosides are sialic acid-containing glycolipids expressed on plasma membranes from nearly all vertebrate cells. The expression of ganglioside GD3, which plays essential roles in normal brain development, decreases in adults but is up regulated in neuroectodermal and epithelial derived cancers. R24 antibody, directed against ganglioside GD3, is a validated tumor target which is specifically endocytosed and accumulated in endosomes. Here, we exploit the internalization feature of the R24 antibody for the selective delivery of saporin, a ribosome-inactivating protein, to GD3-expressing cells [human (SK-Mel-28) and mouse (B16) melanoma cells and Chinese hamster ovary (CHO)-K1 cells]. This immunotoxin showed a specific cytotoxicity on tumor cells grew on 2D monolayers, which was further evident by the lack of any effect on GD3-negative cells. To estimate the potential antitumor activity of R24-saporin complex, we also evaluated the effect of the immunotoxin on the clonogenic growth of SK-Mel-28 and CHO-K1(GD3+) cells cultured in attachment-free conditions. A drastic growth inhibition (>80-90%) of the cell colonies was reached after 3 days of immunotoxin treatment. By the contrary, colonies continue to growth at the same concentration of the immuntoxin, but in the absence of R24 antibody, or in the absence of both immunotoxin and R24, undoubtedly indicating the specificity of the effect observed. Thus, the ganglioside GD3 emerge as a novel and attractive class of cell surface molecule for targeted delivery of cytotoxic agents and, therefore, provides a rationale for future therapeutic intervention in cancer.

  4. Dietary GD3 ganglioside reduces the incidence and severity of necrotizing enterocolitis by sustaining regulatory immune responses.

    PubMed

    Xu, Jiliu; Anderson, Virginia; Schwarz, Steven M

    2013-11-01

    Gangliosides are glycosphingolipids, rich in colostrum and in membrane microdomains, which promote enterocyte growth and differentiation, and modulate TH1/TH2 responses. In an in vitro intestinal explant model of necrotizing enterocolitis (NEC), gangliosides have been shown to ameliorate intestinal injury; however, possible immunomodulatory mechanisms associated with this observation, as well as potential in vivo protective effects of gangliosides, remain unknown. The present study evaluates the effects of dietary GD3, the predominant ganglioside in neonatal rat intestine, both on the clinicopathologic expression of disease and on ileal Foxp3+ T regulatory cell immune responses in an experimental NEC model. Newborn rat pups were fed gavage formula (NEC) or formula supplemented with 15 μg/mL GD3 (GD3-NEC). Dam-fed (DF) littermates served as controls. NEC was induced by asphyxia and cold stress. At 96 hours, ileal gross and histologic changes were evaluated, and ileal cytokine profiles, Foxp3 expression, and Foxp3+ cell numbers were determined. GD3 decreased the incidence and gross and histopathologic severity of NEC. Ileal Foxp3 expression and Foxp3+ cell numbers were significantly decreased in the NEC group compared with DF. GD3 increased ileal Foxp3 expression and Foxp3+ cell numbers, in association with upregulation of anti-inflammatory cytokine interleukin (IL)-10 and chemokines, tissue inhibitor of metalloproteinases 1, IL-1 receptor antagonist (IL-1ra), and suppressed proinflammatory mediators. These data suggest that dietary GD3 protects newborn rats from NEC, in part, by augmenting mucosal Foxp3+ T regulatory immune responses.

  5. Progenitor/Stem Cell Markers in Brain Adjacent to Glioblastoma: GD3 Ganglioside and NG2 Proteoglycan Expression.

    PubMed

    Lama, Gina; Mangiola, Annunziato; Proietti, Gabriella; Colabianchi, Anna; Angelucci, Cristiana; D' Alessio, Alessio; De Bonis, Pasquale; Geloso, Maria Concetta; Lauriola, Libero; Binda, Elena; Biamonte, Filippo; Giuffrida, Maria Grazia; Vescovi, Angelo; Sica, Gigliola

    2016-02-01

    Characterization of tissue surrounding glioblastoma (GBM) is a focus for translational research because tumor recurrence invariably occurs in this area. We investigated the expression of the progenitor/stem cell markers GD3 ganglioside and NG2 proteoglycan in GBM, peritumor tissue (brain adjacent to tumor, BAT) and cancer stem-like cells (CSCs) isolated from GBM (GCSCs) and BAT (PCSCs). GD3 and NG2 immunohistochemistry was performed in paired GBM and BAT specimens from 40 patients. Double-immunofluorescence was carried out to characterize NG2-positive cells of vessel walls. GD3 and NG2 expression was investigated in GCSCs and PCSCs whose tumorigenicity was also evaluated in Scid/bg mice. GD3 and NG2 expression was higher in tumor tissue than in BAT. NG2 decreased as the distance from tumor margin increased, regardless of the tumor cell presence, whereas GD3 correlated with neoplastic infiltration. In BAT, NG2 was coexpressed with a-smooth muscle actin (a-SMA) in pericytes and with nestin in the endothelium. Higher levels of NG2 mRNA and protein were found in GCSCs while GD3 synthase was expressed at similar levels in the 2 CSC populations. PCSCs had lower tumorigenicity than GCSCs. These data suggest the possible involvement of GD3 and NG2 in pre/pro-tumorigenic events occurring in the complex microenvironment of the tissue surrounding GBM.

  6. Ganglioside GD3 as a raft component in cell death regulation.

    PubMed

    Sorice, Maurizio; Garofalo, Tina; Misasi, Roberta; Manganelli, Valeria; Vona, Rosa; Malorni, Walter

    2012-05-01

    Subcellular organelles such as mitochondria, endoplasmic reticulum and the Golgi complex are involved in the progression of cell death program. Recent evidence unveils that Fas ligand-mediated apoptosis induces scrambling of mitochondrial and secretory organelles via a global alteration of membrane traffic that is modulated by apical caspases. On the basis of the biochemical nature of lipid rafts, composed by sphingolipids, including gangliosides and sphingomyelin, cholesterol and signaling proteins, it has been suggested that they are part of this traffic and can participate in cell remodelling leading to cell death program execution. Although detected in various cell types, the role of lipid rafts in apoptosis has been mostly studied in T cells, where the physiological apoptotic program occurs through CD95/Fas. In this review, the possible contribution of lipid rafts to the cascade of events leading to T cell apoptosis after CD95/Fas ligation is summarized. We focused on the paradigmatic component of rafts GD3, which can proceed from the cell plasma membrane (and/or from trans Golgi network) to the mitochondria via a microtubule-dependent mechanism. This transport may be regulated by CLIPR-59, a new CLIP-170-related protein, involved in the regulation of microtubule dynamics. Particular attention has been given to mitochondrial raft-like microdomains, which may represent preferential sites where key reactions take place. Indeed, GD3, by interacting with mitochondrial raft-like microdomains, may trigger specific events involved in the apoptogenic program, including mitochondria hyperpolarization and depolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These findings introduce an additional task for identifying new molecular target(s) of anti-cancer agents.

  7. Ganglioside GD3 Is Required for Neurogenesis and Long-Term Maintenance of Neural Stem Cells in the Postnatal Mouse Brain

    PubMed Central

    Wang, Jing; Cheng, Allison; Wakade, Chandramohan

    2014-01-01

    The maintenance of a neural stem cell (NSC) population in mammalian postnatal and adult life is crucial for continuous neurogenesis and neural repair. However, the molecular mechanism of how NSC populations are maintained remains unclear. Gangliosides are important cellular membrane components in the nervous system. We previously showed that ganglioside GD3 plays a crucial role in the maintenance of the self-renewal capacity of NSCs in vitro. Here, we investigated its role in postnatal and adult neurogenesis in GD3-synthase knock-out (GD3S-KO) and wild-type mice. GD3S-KO mice with deficiency in GD3 and the downstream b-series gangliosides showed a progressive loss of NSCs both at the SVZ and the DG of the hippocampus. The decrease of NSC populations in the GD3S-KO mice resulted in impaired neurogenesis at the granular cell layer of the olfactory bulb and the DG in the adult. In addition, defects of the self-renewal capacity and radial glia-like stem cell outgrowth of postnatal GD3S-KO NSCs could be rescued by restoration of GD3 expression in these cells. Our study demonstrates that the b-series gangliosides, especially GD3, play a crucial role in the long-term maintenance NSC populations in postnatal mouse brain. Moreover, the impaired neurogenesis in the adult GD3S-KO mice led to depression-like behaviors. Thus, our results provide convincing evidence linking b-series gangliosides deficiency and neurogenesis defects to behavioral deficits, and support a crucial role of gangliosides in the long-term maintenance of NSCs in adult mice. PMID:25297105

  8. Ganglioside GD3 is required for neurogenesis and long-term maintenance of neural stem cells in the postnatal mouse brain.

    PubMed

    Wang, Jing; Cheng, Allison; Wakade, Chandramohan; Yu, Robert K

    2014-10-08

    The maintenance of a neural stem cell (NSC) population in mammalian postnatal and adult life is crucial for continuous neurogenesis and neural repair. However, the molecular mechanism of how NSC populations are maintained remains unclear. Gangliosides are important cellular membrane components in the nervous system. We previously showed that ganglioside GD3 plays a crucial role in the maintenance of the self-renewal capacity of NSCs in vitro. Here, we investigated its role in postnatal and adult neurogenesis in GD3-synthase knock-out (GD3S-KO) and wild-type mice. GD3S-KO mice with deficiency in GD3 and the downstream b-series gangliosides showed a progressive loss of NSCs both at the SVZ and the DG of the hippocampus. The decrease of NSC populations in the GD3S-KO mice resulted in impaired neurogenesis at the granular cell layer of the olfactory bulb and the DG in the adult. In addition, defects of the self-renewal capacity and radial glia-like stem cell outgrowth of postnatal GD3S-KO NSCs could be rescued by restoration of GD3 expression in these cells. Our study demonstrates that the b-series gangliosides, especially GD3, play a crucial role in the long-term maintenance NSC populations in postnatal mouse brain. Moreover, the impaired neurogenesis in the adult GD3S-KO mice led to depression-like behaviors. Thus, our results provide convincing evidence linking b-series gangliosides deficiency and neurogenesis defects to behavioral deficits, and support a crucial role of gangliosides in the long-term maintenance of NSCs in adult mice. Copyright © 2014 the authors 0270-6474/14/3413790-11$15.00/0.

  9. Segregation of gangliosides GM1 and GD3 on cell membranes, isolated membrane rafts, and defined supported lipid monolayers.

    PubMed

    Vyas, K A; Patel, H V; Vyas, A A; Schnaar, R L

    2001-02-01

    Lateral assemblies of sphingolipids, glycosphingolipids and cholesterol, termed rafts, are postulated to be present in biological membranes and to function in important cellular phenomena. We probed whether rafts are heterogeneous by determining the relative distribution of two gangliosides, GM1 and GD3, in artificial supported monolayers, in intact rat primary cerebellar granule neurones, and in membrane rafts isolated from rat cerebellum. Fluorescence resonance energy transfer (FRET) using fluorophore-labelled cholera toxin B subunit (which binds GM1) and mAb R24 (which binds GD3) revealed that GM1 spontaneously self-associates but does not co-cluster with GD3 in supported monolayers and on intact neurones. Cholera toxin and immunocytochemical labelling of isolated membrane rafts from rat cerebellum further demonstrated that GM1 does not co-localise with GD3. Furthermore, whereas the membrane raft resident proteins Lyn and caveolin both co-localise with GD3 in isolated membrane rafts, GM1 appears in separate and distinct aggregates. These data support prior reports that membrane rafts are heterogeneous, although the mechanisms for establishing and maintaining such heterogeneity remain to be determined.

  10. Increased a-series gangliosides positively regulate leptin/Ob receptor-mediated signals in hypothalamus of GD3 synthase-deficient mice.

    PubMed

    Ji, Shuting; Tokizane, Kyohei; Ohkawa, Yuki; Ohmi, Yuhsuke; Banno, Ryoichi; Okajima, Tetsuya; Kiyama, Hiroshi; Furukawa, Koichi; Furukawa, Keiko

    2016-10-21

    Gangliosides are widely involved in the regulation of cells and organs. However, little is known about their roles in adipose tissues and hypothalamus. In GD3 synthase-knockout (GD3S KO) mice, deletion of b-series gangliosides resulted in the reduction of serum leptin due to disturbed secretion from adipocytes. To examine whether leptin signals altered, leptin/leptin receptor (ObR)-mediated signaling in hypothalamus was analyzed. Hypothalamus of GD3S KO mouse showed increased expression of GM1 and GD1a, and increased activation of ObR-mediated signals such as pSTAT3 and c-Fos. Leptin stimulation of hypothalamus-derived N-41 cells and their transfectants with GD3S cDNA showed that a-series gangliosides positively regulate leptin/ObR-mediated signals. Co-precipitation analysis revealed that ObR interacts with a-series gangliosides with increased association by leptin stimulation. In brown adipose tissues (BAT) of GD3S KO mice, their weights and adipocyte numbers were increased, and BAT markers such as PGC1α and UCP-1 were also up-regulated. These results suggested that leptin/ObRb-mediated signals were enhanced in hypothalamus of GD3S KO mice due to increased a-series gangliosides, leading to the apparently similar features of energy expenditure between the KO and wild type mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Brain gangliosides of a transgenic mouse model of Alzheimer's disease with deficiency in GD3-synthase: expression of elevated levels of a cholinergic-specific ganglioside, GT1aα

    PubMed Central

    Ariga, Toshio; Itokazu, Yutaka; McDonald, Michael P.; Hirabayashi, Yoshio; Ando, Susumu; Yu, Robert K.

    2013-01-01

    In order to examine the potential involvement of gangliosides in AD (Alzheimer's disease), we compared the ganglioside compositions of the brains of a double-transgenic (Tg) mouse model [APP (amyloid precursor protein)/PSEN1 (presenilin)] of AD and a triple mutant mouse model with an additional deletion of the GD3S (GD3-synthase) gene (APP/PSEN1/GD3S−/−). These animals were chosen since it was previously reported that APP/PSEN1/GD3S−/− triple-mutant mice performed as well as WT (wild-type) control and GD3S−/− mice on a number of reference memory tasks. Cholinergic neuron-specific gangliosides, such as GT1aα and GQ1bα, were elevated in the brains of double-Tg mice (APP/PSEN1), as compared with those of WT mice. Remarkably, in the triple mutant mouse brains (APP/PSEN1/GD3S−/−), the concentration of GT1aα was elevated and as expected there was no expression of GQ1bα. On the other hand, the level of c-series gangliosides, including GT3, was significantly reduced in the double-Tg mouse brain as compared with the WT. Thus, the disruption of the gene of a specific ganglioside-synthase, GD3S, altered the expression of cholinergic neuron-specific gangliosides. Our data thus suggest the intriguing possibility that the elevated cholinergic-specific ganglioside, GT1aα, in the triple mutant mouse brains (APP/PSEN1/GD3S−/−) may contribute to the memory retention in these mice. PMID:23565921

  12. Brain gangliosides of a transgenic mouse model of Alzheimer's disease with deficiency in GD3-synthase: expression of elevated levels of a cholinergic-specific ganglioside, GT1aα.

    PubMed

    Ariga, Toshio; Itokazu, Yutaka; McDonald, Michael P; Hirabayashi, Yoshio; Ando, Susumu; Yu, Robert K

    2013-05-30

    In order to examine the potential involvement of gangliosides in AD (Alzheimer's disease), we compared the ganglioside compositions of the brains of a double-transgenic (Tg) mouse model [APP (amyloid precursor protein)/PSEN1 (presenilin)] of AD and a triple mutant mouse model with an additional deletion of the GD3S (GD3-synthase) gene (APP/PSEN1/GD3S(-/-)). These animals were chosen since it was previously reported that APP/PSEN1/GD3S(-/-) triple-mutant mice performed as well as WT (wild-type) control and GD3S(-/-) mice on a number of reference memory tasks. Cholinergic neuron-specific gangliosides, such as GT1aα and GQ1bα, were elevated in the brains of double-Tg mice (APP/PSEN1), as compared with those of WT mice. Remarkably, in the triple mutant mouse brains (APP/PSEN1/GD3S(-/-)), the concentration of GT1aα was elevated and as expected there was no expression of GQ1bα. On the other hand, the level of c-series gangliosides, including GT3, was significantly reduced in the double-Tg mouse brain as compared with the WT. Thus, the disruption of the gene of a specific ganglioside-synthase, GD3S, altered the expression of cholinergic neuron-specific gangliosides. Our data thus suggest the intriguing possibility that the elevated cholinergic-specific ganglioside, GT1aα, in the triple mutant mouse brains (APP/PSEN1/GD3S(-/-)) may contribute to the memory retention in these mice.

  13. UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor α and interleukin 6.

    PubMed

    Miyata, Maiko; Ichihara, Masatoshi; Tajima, Orie; Sobue, Sayaka; Kambe, Mariko; Sugiura, Kazumitsu; Furukawa, Koichi; Furukawa, Keiko

    2014-03-07

    Although expression of gangliosides and their synthetic enzyme genes in malignant melanomas has been well studied, that in normal melanocytes has been scarcely analyzed. In particular, changes in expression levels of glycosyltransferase genes responsible for ganglioside synthesis during evolution of melanomas from melanocytes are very important to understand roles of gangliosides in melanomas. Here, expression of glycosyltransferase genes related to the ganglioside synthesis was analyzed using RNAs from cultured melanocytes and melanoma cell lines. Quantitative RT-PCR revealed that melanomas expressed high levels of mRNA of GD3 synthase and GM2/GD2 synthase genes and low levels of GM1/GD1b synthase genes compared with melanocytes. As a representative exogenous stimulation, effects of ultraviolet B (UVB) on the expression levels of 3 major ganglioside synthase genes in melanocytes were analyzed. Although direct UVB irradiation of melanocytes caused no marked changes, culture supernatants of UVB-irradiated keratinocytes (HaCaT cells) induced definite up-regulation of GD3 synthase and GM2/GD2 synthase genes. Detailed examination of the supernatants revealed that inflammatory cytokines such as TNFα and IL-6 enhanced GD3 synthase gene expression. These results suggest that inflammatory cytokines secreted from UVB-irradiated keratinocytes induced melanoma-associated ganglioside synthase genes, proposing roles of skin microenvironment in the promotion of melanoma-like ganglioside profiles in melanocytes.

  14. Ganglioside GD3 Enhances Invasiveness of Gliomas by Forming a Complex with Platelet-derived Growth Factor Receptor α and Yes Kinase.

    PubMed

    Ohkawa, Yuki; Momota, Hiroyuki; Kato, Akira; Hashimoto, Noboru; Tsuda, Yusuke; Kotani, Norihiro; Honke, Koichi; Suzumura, Akio; Furukawa, Keiko; Ohmi, Yuhsuke; Natsume, Atsushi; Wakabayashi, Toshihiko; Furukawa, Koichi

    2015-06-26

    There have been a few studies on the ganglioside expression in human glioma tissues. However, the role of these gangliosides such as GD3 and GD2 has not been well understood. In this study we employed a genetically engineered mouse model of glioma to clarify the functions of GD3 in gliomas. Forced expression of platelet-derived growth factor B in cultured astrocytes derived from p53-deficient mice resulted in the expression of GD3 and GD2. GD3-positive astrocytes exhibited increased cell growth and invasion activities along with elevated phosphorylation of Akt and Yes kinase. By enzyme-mediated activation of radical sources reaction and mass spectrometry, we identified PDGF receptor α (PDGFRα) as a GD3-associated molecule. GD3-positive astrocytes showed a significant amount of PDGFRα in glycolipid-enriched microdomains/rafts compared with GD3-negative cells. Src kinase family Yes was co-precipitated with PDGFRα, and its pivotal role in the increased cell invasion of GD3-positive astrocytes was demonstrated by silencing with anti-Yes siRNA. Direct association between PDGFRα and GD3 was also shown, suggesting that GD3 forms ternary complex with PDGFRα and Yes. The fact that GD3, PDGFRα, and activated Yes were colocalized in lamellipodia and the edge of tumors in cultured cells and glioma tissues, respectively, suggests that GD3 induced by platelet-derived growth factor B enhances PDGF signals in glycolipid-enriched microdomain/rafts, leading to the promotion of malignant phenotypes such as cell proliferation and invasion in gliomas.

  15. Ganglioside GD3 Enhances Invasiveness of Gliomas by Forming a Complex with Platelet-derived Growth Factor Receptor α and Yes Kinase*

    PubMed Central

    Ohkawa, Yuki; Momota, Hiroyuki; Kato, Akira; Hashimoto, Noboru; Tsuda, Yusuke; Kotani, Norihiro; Honke, Koichi; Suzumura, Akio; Furukawa, Keiko; Ohmi, Yuhsuke; Natsume, Atsushi; Wakabayashi, Toshihiko; Furukawa, Koichi

    2015-01-01

    There have been a few studies on the ganglioside expression in human glioma tissues. However, the role of these gangliosides such as GD3 and GD2 has not been well understood. In this study we employed a genetically engineered mouse model of glioma to clarify the functions of GD3 in gliomas. Forced expression of platelet-derived growth factor B in cultured astrocytes derived from p53-deficient mice resulted in the expression of GD3 and GD2. GD3-positive astrocytes exhibited increased cell growth and invasion activities along with elevated phosphorylation of Akt and Yes kinase. By enzyme-mediated activation of radical sources reaction and mass spectrometry, we identified PDGF receptor α (PDGFRα) as a GD3-associated molecule. GD3-positive astrocytes showed a significant amount of PDGFRα in glycolipid-enriched microdomains/rafts compared with GD3-negative cells. Src kinase family Yes was co-precipitated with PDGFRα, and its pivotal role in the increased cell invasion of GD3-positive astrocytes was demonstrated by silencing with anti-Yes siRNA. Direct association between PDGFRα and GD3 was also shown, suggesting that GD3 forms ternary complex with PDGFRα and Yes. The fact that GD3, PDGFRα, and activated Yes were colocalized in lamellipodia and the edge of tumors in cultured cells and glioma tissues, respectively, suggests that GD3 induced by platelet-derived growth factor B enhances PDGF signals in glycolipid-enriched microdomain/rafts, leading to the promotion of malignant phenotypes such as cell proliferation and invasion in gliomas. PMID:25940087

  16. Interaction of ganglioside GD3 with an EGF receptor sustains the self-renewal ability of mouse neural stem cells in vitro

    PubMed Central

    Wang, Jing; Yu, Robert K.

    2013-01-01

    Mounting evidence supports the notion that gangliosides serve regulatory roles in neurogenesis; little is known, however, about how these glycosphingolipids function in neural stem cell (NSC) fate determination. We previously demonstrated that ganglioside GD3 is a major species in embryonic mouse brain: more than 80% of the NSCs obtained by the neurosphere method express GD3. To investigate the functional role of GD3 in neurogenesis, we compared the properties of NSCs from GD3-synthase knockout (GD3S-KO) mice with those from their wild-type littermates. NSCs from GD3S-KO mice showed decreased self-renewal ability compared with those from the wild-type animals, and that decreased ability was accompanied by reduced expression of EGF receptor (EGFR) and an increased degradation rate of EGFR and EGF-induced ERK signaling. We also showed that EGFR switched from the low-density lipid raft fractions in wild-type NSCs to the high-density layers in the GD3S-KO NSCs. Immunochemical staining revealed colocalization of EGFR and GD3, and EGFR could be immunoprecipitated from the NSC lysate with an anti-GD3 antibody from the wild-type, but not from the GD3S-KO, mice. Tracking the localization of endocytosed EGFR with endocytosis pathway markers indicated that more EGFR in GD3S-KO NSCs translocated through the endosomal−lysosomal degradative pathway, rather than through the recycling pathway. Those findings support the idea that GD3 interacts with EGFR in the NSCs and that the interaction is responsible for sustaining the expression of EGFR and its downstream signaling to maintain the self-renewal capability of NSCs. PMID:24198336

  17. Interaction of ganglioside GD3 with an EGF receptor sustains the self-renewal ability of mouse neural stem cells in vitro.

    PubMed

    Wang, Jing; Yu, Robert K

    2013-11-19

    Mounting evidence supports the notion that gangliosides serve regulatory roles in neurogenesis; little is known, however, about how these glycosphingolipids function in neural stem cell (NSC) fate determination. We previously demonstrated that ganglioside GD3 is a major species in embryonic mouse brain: more than 80% of the NSCs obtained by the neurosphere method express GD3. To investigate the functional role of GD3 in neurogenesis, we compared the properties of NSCs from GD3-synthase knockout (GD3S-KO) mice with those from their wild-type littermates. NSCs from GD3S-KO mice showed decreased self-renewal ability compared with those from the wild-type animals, and that decreased ability was accompanied by reduced expression of EGF receptor (EGFR) and an increased degradation rate of EGFR and EGF-induced ERK signaling. We also showed that EGFR switched from the low-density lipid raft fractions in wild-type NSCs to the high-density layers in the GD3S-KO NSCs. Immunochemical staining revealed colocalization of EGFR and GD3, and EGFR could be immunoprecipitated from the NSC lysate with an anti-GD3 antibody from the wild-type, but not from the GD3S-KO, mice. Tracking the localization of endocytosed EGFR with endocytosis pathway markers indicated that more EGFR in GD3S-KO NSCs translocated through the endosomal-lysosomal degradative pathway, rather than through the recycling pathway. Those findings support the idea that GD3 interacts with EGFR in the NSCs and that the interaction is responsible for sustaining the expression of EGFR and its downstream signaling to maintain the self-renewal capability of NSCs.

  18. A liquid chromatography/tandem mass spectrometric approach for the determination of gangliosides GD3 and GM3 in bovine milk and infant formulae.

    PubMed

    Sørensen, Lambert K

    2006-01-01

    A liquid chromatographic/tandem mass spectrometric method using pneumatically assisted electrospray ionisation (LC/ESI-MS/MS) was developed for the determination of gangliosides GD3 and GM3 in milk and infant formulae. The gangliosides were extracted in a chloroform/methanol/water environment and cleaned up by solid-phase extraction (SPE) on an end-capped C8 sorbent. The gangliosides were detected in negative ion mode after separation on a reversed-phase (RP) C5 analytical column. From the different ganglioside molecular species, product ions at m/z 290 corresponding to an N-acetylneuraminic acid fragment were produced in the collision cell and used in selected reaction monitoring. A standard addition technique was applied for quantification. The relative repeatability standard deviations were less than 5% for GD3 (level 10 mg/L) and 14% for GM3 (level 0.1-0.2 mg/L). Copyright 2006 John Wiley & Sons, Ltd.

  19. UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor α and interleukin 6

    SciTech Connect

    Miyata, Maiko; Ichihara, Masatoshi; Tajima, Orie; Sobue, Sayaka; Kambe, Mariko; Sugiura, Kazumitsu; Furukawa, Koichi; Furukawa, Keiko

    2014-03-07

    Highlights: • Melanocytes showed low ST8SIA1 and high B3GALT4 levels in contrast with melanomas. • Direct UVB irradiation of melanocytes did not induce ganglioside synthase genes. • Culture supernatants of UVB-irradiated keratinocytes induced ST8SIA1 in melanocytes. • TNFα and IL-6 secreted from keratinocytes enhanced ST8SIA1 expression in melanocytes. • Inflammatory cytokines induced melanoma-related ST8SIA1 in melanocytes. - Abstract: Although expression of gangliosides and their synthetic enzyme genes in malignant melanomas has been well studied, that in normal melanocytes has been scarcely analyzed. In particular, changes in expression levels of glycosyltransferase genes responsible for ganglioside synthesis during evolution of melanomas from melanocytes are very important to understand roles of gangliosides in melanomas. Here, expression of glycosyltransferase genes related to the ganglioside synthesis was analyzed using RNAs from cultured melanocytes and melanoma cell lines. Quantitative RT-PCR revealed that melanomas expressed high levels of mRNA of GD3 synthase and GM2/GD2 synthase genes and low levels of GM1/GD1b synthase genes compared with melanocytes. As a representative exogenous stimulation, effects of ultraviolet B (UVB) on the expression levels of 3 major ganglioside synthase genes in melanocytes were analyzed. Although direct UVB irradiation of melanocytes caused no marked changes, culture supernatants of UVB-irradiated keratinocytes (HaCaT cells) induced definite up-regulation of GD3 synthase and GM2/GD2 synthase genes. Detailed examination of the supernatants revealed that inflammatory cytokines such as TNFα and IL-6 enhanced GD3 synthase gene expression. These results suggest that inflammatory cytokines secreted from UVB-irradiated keratinocytes induced melanoma-associated ganglioside synthase genes, proposing roles of skin microenvironment in the promotion of melanoma-like ganglioside profiles in melanocytes.

  20. Ganglioside GD3 enhances adhesion signals and augments malignant properties of melanoma cells by recruiting integrins to glycolipid-enriched microdomains.

    PubMed

    Ohkawa, Yuki; Miyazaki, Sayaka; Hamamura, Kazunori; Kambe, Mariko; Miyata, Maiko; Tajima, Orie; Ohmi, Yuhsuke; Yamauchi, Yoshio; Furukawa, Koichi; Furukawa, Keiko

    2010-08-27

    Ganglioside GD3 is widely expressed in human malignant melanoma cell lines and tumors. Previously, we reported that GD3+ cells show stronger tyrosine phosphorylation of focal adhesion kinase (FAK), p130(Cas), and paxillin when treated with fetal calf serum than GD3- cells. In this study, we analyzed the changes in the signals mediated by the interaction between integrins and extracellular matrices (ECM) to clarify how GD3 enhances cell signals in the vicinity of the cell membrane. An adhesion assay with a real time cell electronic sensing system revealed that GD3+ cells had stronger adhesion to all extracellular matrices examined. In particular, GD3+ cells attached more strongly to collagen type I and type IV than controls. Correspondingly, they showed stronger tyrosine phosphorylation of FAK and paxillin during adhesion to collagen type I. In the floating pattern of detergent extracts, a high level of integrin beta1 was found in glycolipid-enriched microdomain (GEM)/rafts in GD3+ cells before adhesion, whereas a smaller amount of integrin beta1 was detected in the GEM/rafts of controls. Some phosphorylated forms of FAK as well as total FAK were found in GEM/rafts during cell adhesion only in GD3+ cells. Another signal consisting of integrin-linked kinase/Akt was also activated during adhesion more strongly in GD3+ cells than in controls. In double stained GD3+ cells, GD3 and integrin beta1 co-localized at the focal adhesion with a punctate pattern. All these results suggested that integrins assembled and formed a cluster in GEM/rafts, leading to the enhanced signaling and malignant properties under GD3 expression.

  1. 9-O-Acetylation of sialic acids is catalysed by CASD1 via a covalent acetyl-enzyme intermediate

    PubMed Central

    Baumann, Anna-Maria T.; Bakkers, Mark J. G.; Buettner, Falk F. R.; Hartmann, Maike; Grove, Melanie; Langereis, Martijn A.; de Groot, Raoul J.; Mühlenhoff, Martina

    2015-01-01

    Sialic acids, terminal sugars of glycoproteins and glycolipids, play important roles in development, cellular recognition processes and host–pathogen interactions. A common modification of sialic acids is 9-O-acetylation, which has been implicated in sialoglycan recognition, ganglioside biology, and the survival and drug resistance of acute lymphoblastic leukaemia cells. Despite many functional implications, the molecular basis of 9-O-acetylation has remained elusive thus far. Following cellular approaches, including selective gene knockout by CRISPR/Cas genome editing, we here show that CASD1—a previously identified human candidate gene—is essential for sialic acid 9-O-acetylation. In vitro assays with the purified N-terminal luminal domain of CASD1 demonstrate transfer of acetyl groups from acetyl-coenzyme A to CMP-activated sialic acid and formation of a covalent acetyl-enzyme intermediate. Our study provides direct evidence that CASD1 is a sialate O-acetyltransferase and serves as key enzyme in the biosynthesis of 9-O-acetylated sialoglycans. PMID:26169044

  2. Fine specificity of natural killer T cells against GD3 ganglioside and identification of GM3 as an inhibitory natural killer T-cell ligand.

    PubMed

    Park, Jun-Eui; Wu, Dianna Y; Prendes, Maria; Lu, Sharon X; Ragupathi, Govind; Schrantz, Nicolas; Chapman, Paul B

    2008-01-01

    GD3, a ganglioside expressed on melanoma, is the only tumour-associated glycolipid described to date that can induce a CD1d-restricted natural killer T (NKT)-cell response. We analysed the fine specificity of GD3-reactive NKT cells and discovered that immunization with GD3 induced two populations of GD3-reactive NKT cells. One population was CD4+ CD8- and was specific for GD3; the other population was CD4- CD8- and cross-reacted with GM3 in a CD1d-restricted manner, but did not cross-react with GM2, GD2, or lactosylceramide. This indicated that the T-cell receptors reacting with GD3 recognize glucose-galactose linked to at least one N-acetyl-neuraminic acid but will not accommodate a terminal N-acetylgalactosamine. Immunization with GM2, GM3, GD2, or lactosylceramide did not induce an NKT-cell response. Coimmunization of GM3-loaded antigen-presenting cells (APCs) with GD3-loaded APCs suppressed the NKT-cell response to GD3 in a CD1d-restricted manner. This suppressive effect was specific for GM3 and was a local effect lasting 2-4 days. In vitro, GM3-loaded APCs also suppressed the interleukin-4 response, but not the interferon-gamma response, of NKT cells to alpha-galactosylceramide. However, there was no effect on the T helper type 2 responses of conventional T cells. We found that this suppression was not mediated by soluble factors. We hypothesize that GM3 induces changes to the APC that lead to suppression of T helper type 2-like NKT-cell responses.

  3. Accumulation of unusual gangliosides G(Q3) and G(P3) in breast cancer cells expressing the G(D3) synthase.

    PubMed

    Steenackers, Agata; Vanbeselaere, Jorick; Cazet, Aurélie; Bobowski, Marie; Rombouts, Yoann; Colomb, Florent; Le Bourhis, Xuefen; Guérardel, Yann; Delannoy, Philippe

    2012-08-10

    Glycosphingolipids from the ganglio-series are usually classified in four series according to the presence of 0 to 3 sialic acid residues linked to lactosylceramide. The transfer of sialic acid is catalyzed in the Golgi apparatus by specific sialyltransferases that show high specificity toward glycolipid substrates. ST8Sia I (EC 2.4.99.8, SAT-II, SIAT 8a) is the key enzyme controlling the biosynthesis of b- and c-series gangliosides. ST8Sia I is expressed at early developmental stages whereas in adult human tissues, ST8Sia I transcripts are essentially detected in brain. ST8Sia I together with b- and c-series gangliosides are also over-expressed in neuroectoderm-derived malignant tumors such as melanoma, glioblastoma, neuroblastoma and in estrogen receptor (ER) negative breast cancer, where they play a role in cell proliferation, migration, adhesion and angiogenesis. We have stably expressed ST8Sia I in MCF-7 breast cancer cells and analyzed the glycosphingolipid composition of wild type (WT) and GD3S+ clones. As shown by mass spectrometry, MCF-7 expressed a complex pattern of neutral and sialylated glycosphingolipids from globo- and ganglio-series. WT MCF-7 cells exhibited classical monosialylated gangliosides including G(M3), G(M2), and G(M1a). In parallel, the expression of ST8Sia I in MCF-7 GD3S+ clones resulted in a dramatic change in ganglioside composition, with the expression of b- and c-series gangliosides as well as unusual tetra- and pentasialylated lactosylceramide derivatives G(Q3) (II(3)Neu5Ac(4)-Gg(2)Cer) and G(P3) (II(3)Neu5Ac(5)-Gg(2)Cer). This indicates that ST8Sia I is able to act as an oligosialyltransferase in a cellular context.

  4. Biosynthesis and turnover of O-acetyl and N-acetyl groups in the gangliosides of human melanoma cells

    SciTech Connect

    Manzi, A.E.; Sjoberg, E.R.; Diaz, S.; Varki, A.

    1990-08-05

    We and others previously described the melanoma-associated oncofetal glycosphingolipid antigen 9-O-acetyl-GD3, a disialoganglioside O-acetylated at the 9-position of the outer sialic acid residue. We have now developed methods to examine the biosynthesis and turnover of disialogangliosides in cultured melanoma cells and in Golgi-enriched vesicles from these cells. O-Acetylation was selectively expressed on di- and trisialogangliosides, but not on monosialogangliosides, nor on glycoprotein-bound sialic acids. Double-labeling of cells with (3H)acetate and (14C)glucosamine introduced easily detectable labels into each of the components of the ganglioside molecules. Pulse-chase studies of such doubly labeled molecules indicated that the O-acetyl groups turn over faster than the parent molecule. When Golgi-enriched vesicles from these cells were incubated with (acetyl-3H)acetyl-coenzyme A, the major labeled products were disialogangliosides. (Acetyl-3H)O-acetyl groups were found at both the 7- and the 9-positions, indicating that both 7-O-acetyl GD3 and 9-O-acetyl GD3 were synthesized by the action of O-acetyltransferase(s) on endogenous GD3. Analysis of the metabolically labeled molecules confirmed the existence of both 7- and 9-O-acetylated GD3 in the intact cells. Surprisingly, the major 3H-labeled product of the in vitro labeling reaction was not O-acetyl-GD3, but GD3, with the label exclusively in the sialic acid residues. Fragmentation of the labeled sialic acids by enzymatic and chemical methods showed that the 3H-label was exclusively in (3H)N-acetyl groups. Analyses of the double-labeled sialic acids from intact cells also showed that the 3H-label from (3H)acetate was exclusively in the form of (3H)N-acetyl groups, whereas the 14C-label was at the 4-position.

  5. A therapeutic trial of human melanomas with combined small interfering RNAs targeting adaptor molecules p130Cas and paxillin activated under expression of ganglioside GD3.

    PubMed

    Makino, Yusuke; Hamamura, Kazunori; Takei, Yoshifumi; Bhuiyan, Robiul Hasan; Ohkawa, Yuki; Ohmi, Yuhsuke; Nakashima, Hideyuki; Furukawa, Keiko; Furukawa, Koichi

    2016-08-01

    We previously demonstrated that focal adhesion kinase (FAK), p130Cas and paxillin are crucially involved in the enhanced malignant properties under expression of ganglioside GD3 in melanoma cells. Therefore, molecules existing in the GD3-mediated signaling pathway could be considered as suitable targets for therapeutic intervention in malignant melanoma. The aim of this study was to determine whether blockade of p130Cas and/or paxillin by RNAi suppresses melanoma growth. We found a suitable dose (40 μM siRNA, 25 μl/tumor) of the siRNA to suppress p130Cas in the xenografts generated in nu/nu mice. Based on these results, we performed intratumoral (i.t.) treatment with anti-p130Cas and/or anti-paxillin siRNAs mixed with atelocollagen as a drug delivery system in a xenograft tumor of a human melanoma cell line, SK-MEL-28. Mixture of atelocollagen (1.75%) and an siRNA (500 or 1000 pmol/tumor) was injected into the tumors every 3 days after the first injection. An siRNA against human p130Cas markedly suppressed tumor growth of the xenograft in a dose-dependent manner, whereas siRNA against human paxillin slightly inhibited the tumor growth. A control siRNA against firefly luciferase showed no effect. To our surprise, siRNA against human p130Cas (500 or 1000 pmol/tumor) combined with siRNA against human paxillin dramatically suppressed tumor growth. In agreement with the tumor suppression effects of the anti-p130Cas siRNA, reduction in Ki-67 positive cell number as well as in p130Cas expression was demonstrated by immunohistostaining. These results suggested that blockade of GD3-mediated growth signaling pathways by siRNAs might be a novel and promising therapeutic strategy against malignant melanomas, provided signaling molecules such as p130Cas and paxillin are significantly expressed in individual cases. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc. Copyright © 2016 Elsevier B.V. All rights

  6. Functional Activation of Src Family Kinase Yes Protein Is Essential for the Enhanced Malignant Properties of Human Melanoma Cells Expressing Ganglioside GD3*

    PubMed Central

    Hamamura, Kazunori; Tsuji, Momoko; Hotta, Hiroshi; Ohkawa, Yuki; Takahashi, Masataka; Shibuya, Hidenobu; Nakashima, Hideyuki; Yamauchi, Yoshio; Hashimoto, Noboru; Hattori, Hisashi; Ueda, Minoru; Furukawa, Keiko; Furukawa, Koichi

    2011-01-01

    The possible roles of Src family kinases in the enhanced malignant properties of melanomas related to GD3 expression were analyzed. Among Src family kinases only Yes, not Fyn or Src, was functionally involved in the increased cell proliferation and invasion of GD3-expressing transfectant cells (GD3+). Yes was located upstream of p130Cas and paxillin and at an equivalent level to focal adhesion kinase. Yes underwent autophosphorylation even before serum treatment and showed stronger kinase activity in GD3+ cells than in GD3− cells following serum treatment. Coimmunoprecipitation experiments revealed that Yes bound to focal adhesion kinase or p130Cas more strongly in GD3+ cells than in GD3− cells. As a possible mechanism for the enhancing effects of GD3 on cellular phenotypes, it was shown that majority of Yes was localized in glycolipid-enriched microdomain/rafts in GD3+ cells even before serum treatment, whereas it was scarcely detected in glycolipid-enriched microdomain/rafts in GD3− cells. An in vitro kinase assay of Yes revealed that coexistence of GD3 with Yes in membranous environments enhances the kinase activity of GD3− cell-derived Yes toward enolase, p125, and Yes itself. Knockdown of GD3 synthase resulted in the alleviation of tumor phenotypes and reduced activation levels of Yes. Taken together, these results suggest a role of GD3 in the regulation of Src family kinases. PMID:21454696

  7. Functional activation of Src family kinase yes protein is essential for the enhanced malignant properties of human melanoma cells expressing ganglioside GD3.

    PubMed

    Hamamura, Kazunori; Tsuji, Momoko; Hotta, Hiroshi; Ohkawa, Yuki; Takahashi, Masataka; Shibuya, Hidenobu; Nakashima, Hideyuki; Yamauchi, Yoshio; Hashimoto, Noboru; Hattori, Hisashi; Ueda, Minoru; Furukawa, Keiko; Furukawa, Koichi

    2011-05-27

    The possible roles of Src family kinases in the enhanced malignant properties of melanomas related to GD3 expression were analyzed. Among Src family kinases only Yes, not Fyn or Src, was functionally involved in the increased cell proliferation and invasion of GD3-expressing transfectant cells (GD3+). Yes was located upstream of p130Cas and paxillin and at an equivalent level to focal adhesion kinase. Yes underwent autophosphorylation even before serum treatment and showed stronger kinase activity in GD3+ cells than in GD3- cells following serum treatment. Coimmunoprecipitation experiments revealed that Yes bound to focal adhesion kinase or p130Cas more strongly in GD3+ cells than in GD3- cells. As a possible mechanism for the enhancing effects of GD3 on cellular phenotypes, it was shown that majority of Yes was localized in glycolipid-enriched microdomain/rafts in GD3+ cells even before serum treatment, whereas it was scarcely detected in glycolipid-enriched microdomain/rafts in GD3- cells. An in vitro kinase assay of Yes revealed that coexistence of GD3 with Yes in membranous environments enhances the kinase activity of GD3- cell-derived Yes toward enolase, p125, and Yes itself. Knockdown of GD3 synthase resulted in the alleviation of tumor phenotypes and reduced activation levels of Yes. Taken together, these results suggest a role of GD3 in the regulation of Src family kinases.

  8. Isotopic labeling of milk disialogangliosides (GD3).

    PubMed

    Reis, Mariza Gomes; Bibiloni, Rodrigo; McJarrow, Paul; MacGibbon, Alastair; Fong, Bertram; Bassett, Shalome; Roy, Nicole; Dos Reis, Marlon Martins

    2016-10-01

    The most abundant ganglioside group in both human milk and bovine milk during the first postnatal week is ganglioside GD3. This group of disialogangliosides forms up to 80% of the total ganglioside content of colostrum. Although dietary gangliosides have shown biological activity such as improvement of cognitive development, gastrointestinal health, and immune function, there is still a gap in our understanding of the molecular mechanisms governing its uptake and the metabolic processes affecting its bioavailability. The use of isotopically labeled ganglioside to track the bioavailability, absorption, distribution, and metabolism of gangliosides may provide key information to bridge this gap. However, isotope labeled GD3 is not commercially available and its preparation has not been described. We report for the first time the preparation of labeled GD3 with stable isotopes. Using alkaline hydrolysis, we were able to selectively remove both acetyl groups from the tetrasaccharide portion of GD3 without promoting significant hydrolysis of the ceramide portion of the molecule to generate N-deacetyl-GD3 (Neu5α2-8Neu5-GD3). The N-deacetyl-GD3 was then chemoselectively re-acetylated in aqueous medium using deuterated acetic anhydride in the presence of Triton X 100 to produce (2)H6-GD3 {GD3[(Neu5Ac-11-(2)H3)-(Neu5Ac-11-(2)H3)]}. This method provided (2)H6-GD3 with approximately 60% yield. This compound was characterized by proton nuclear magnetic resonance ((1)H NMR) and liquid chromatography mass spectrometry (LC-MS). The oral absorption of the (2)H6-GD3 was demonstrated using a Sprague-Dawley weaning rats. Our results indicate that some ingested labeled milk gangliosides are absorbed and transported into the bloodstream without modification. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Ganglioside biosynthesis in developing brains and apoptotic cancer cells: X. regulation of glyco-genes involved in GD3 and Sialyl-Lex/a syntheses.

    PubMed

    Basu, Subhash; Ma, Rui; Moskal, Joseph R; Basu, Manju

    2012-06-01

    Gangliosides, the acidic glycosphingolipids (GSLs) containing N-acetylgalactosamine and sialic acid are ubiquitous in the central nervous system. At least six DSL-glycosyltransferase activities (GLTs Gangliosides, the acidic glycosphingolipids (GSLs) containing N-acetylgalactosamine and sialic acid (or NAc-Neuraminic acid) are ubiquitous in the central nervous system. At least six GSL-glycosyltransferase activities (GLTs) of Basu-Roseman pathway catalyzing the biosynthesis of these gangliosides have been characterized in developing chicken brains. Most of these glyco-genes are expressed in the early stages (7-17 days) of brain development and lowered in the adult stage, but the cause of reduction of enzymatic activities of these GLTs in the adult stages is not known. In order to study glyco-gene regulation we used four clonal metastatic cancer cells of colon and breast cancer tissue origin (Colo-205, SKBR-3, MDA-468, and MCF-3). The glyco-genes for synthesis of SA-LeX and SA-LeA (which contain N-acetylglucosamine, sialic acid and fucose) in these cells were modulated differently at different phases (between 2 and 48 h) of apoptotic inductions. L-PPMP, D-PDMP (inhibitor of glucosylceramide biosynthesis), Betulinic Acid (a triterpinoid isolated from bark of certain trees and used for cancer treatment in China), Tamoxifen a drug in use in the west for treatment of early stages of the disease in breast cancer patients), and cis-platin (an inhibitor of DNA biosynthesis used for testicular cancer patients) were used for induction of apoptosis in the above-mentioned cell lines. Within 2-6 h, transcriptional modulation of a number of glyco-genes was observed by DNA-micro-array (containing over 300 glyco genes attached to the glass cover slips) studies. Under long incubation time (24-48 h) almost all of the glyco-genes were downregulated. The cause of these glyco-gene regulations during apoptotic induction in metastatic carcinoma cells is unknown and needs future

  10. Glycolipid GD3 and GD3 synthase are key drivers for glioblastoma stem cells and tumorigenicity

    PubMed Central

    Yeh, Shih-Chi; Wang, Pao-Yuan; Lou, Yi-Wei; Khoo, Kay-Hooi; Hsiao, Michael; Hsu, Tsui-Ling; Wong, Chi-Huey

    2016-01-01

    The cancer stem cells (CSCs) of glioblastoma multiforme (GBM), a grade IV astrocytoma, have been enriched by the expressed marker CD133. However, recent studies have shown that CD133− cells also possess tumor-initiating potential. By analysis of gangliosides on various cells, we show that ganglioside D3 (GD3) is overexpressed on eight neurospheres and tumor cells; in combination with CD133, the sorted cells exhibit a higher expression of stemness genes and self-renewal potential; and as few as six cells will form neurospheres and 20–30 cells will grow tumor in mice. Furthermore, GD3 synthase (GD3S) is increased in neurospheres and human GBM tissues, but not in normal brain tissues, and suppression of GD3S results in decreased GBM stem cell (GSC)-associated properties. In addition, a GD3 antibody is shown to induce complement-dependent cytotoxicity against cells expressing GD3 and inhibition of GBM tumor growth in vivo. Our results demonstrate that GD3 and GD3S are highly expressed in GSCs, play a key role in glioblastoma tumorigenicity, and are potential therapeutic targets against GBM. PMID:27143722

  11. Glycolipid GD3 and GD3 synthase are key drivers for glioblastoma stem cells and tumorigenicity.

    PubMed

    Yeh, Shih-Chi; Wang, Pao-Yuan; Lou, Yi-Wei; Khoo, Kay-Hooi; Hsiao, Michael; Hsu, Tsui-Ling; Wong, Chi-Huey

    2016-05-17

    The cancer stem cells (CSCs) of glioblastoma multiforme (GBM), a grade IV astrocytoma, have been enriched by the expressed marker CD133. However, recent studies have shown that CD133(-) cells also possess tumor-initiating potential. By analysis of gangliosides on various cells, we show that ganglioside D3 (GD3) is overexpressed on eight neurospheres and tumor cells; in combination with CD133, the sorted cells exhibit a higher expression of stemness genes and self-renewal potential; and as few as six cells will form neurospheres and 20-30 cells will grow tumor in mice. Furthermore, GD3 synthase (GD3S) is increased in neurospheres and human GBM tissues, but not in normal brain tissues, and suppression of GD3S results in decreased GBM stem cell (GSC)-associated properties. In addition, a GD3 antibody is shown to induce complement-dependent cytotoxicity against cells expressing GD3 and inhibition of GBM tumor growth in vivo. Our results demonstrate that GD3 and GD3S are highly expressed in GSCs, play a key role in glioblastoma tumorigenicity, and are potential therapeutic targets against GBM.

  12. Ganglioside patterns in human spinal cord.

    PubMed

    Vorwerk, C K

    2001-12-01

    To examine the distribution of gangliosides in human cervical and lumbar spinal cord. Magdeburg, Germany. The ganglioside distribution of human cervical and lumbar spinal cord enlargements from 10 neurological normal patients was analyzed. Gangliosides were isolated from different areas corresponding to the columna anterior, columna lateralis and columna posterior. Ganglioside GfD1b/GD1b and GD3 were the most abundant gangliosides in all examined tissues. The total concentration of sialic acid bound gangliosides GM2 and GM3 was less than 5%. The GD3 fraction constantly consisted of a double band as assessed by TLC after lipid extraction. There were significant differences in the ganglioside distribution when comparing tissue from the columna anterior, columna lateralis and columna posterior of the lumbar enlargement of the spinal cord. Differences in the ganglioside composition in human spinal cord regions may reflect the different function of those molecules in the two regions investigated.

  13. Amyloid Precursor Protein (APP) Mediated Regulation of Ganglioside Homeostasis Linking Alzheimer's Disease Pathology with Ganglioside Metabolism

    PubMed Central

    Grimm, Marcus O. W.; Zinser, Eva G.; Grösgen, Sven; Hundsdörfer, Benjamin; Rothhaar, Tatjana L.; Burg, Verena K.; Kaestner, Lars; Bayer, Thomas A.; Lipp, Peter; Müller, Ulrike; Grimm, Heike S.; Hartmann, Tobias

    2012-01-01

    Gangliosides are important players for controlling neuronal function and are directly involved in AD pathology. They are among the most potent stimulators of Aβ production, are enriched in amyloid plaques and bind amyloid beta (Aβ). However, the molecular mechanisms linking gangliosides with AD are unknown. Here we identified the previously unknown function of the amyloid precursor protein (APP), specifically its cleavage products Aβ and the APP intracellular domain (AICD), of regulating GD3-synthase (GD3S). Since GD3S is the key enzyme converting a- to b-series gangliosides, it therefore plays a major role in controlling the levels of major brain gangliosides. This regulation occurs by two separate and additive mechanisms. The first mechanism directly targets the enzymatic activity of GD3S: Upon binding of Aβ to the ganglioside GM3, the immediate substrate of the GD3S, enzymatic turnover of GM3 by GD3S was strongly reduced. The second mechanism targets GD3S expression. APP cleavage results, in addition to Aβ release, in the release of AICD, a known candidate for gene transcriptional regulation. AICD strongly down regulated GD3S transcription and knock-in of an AICD deletion mutant of APP in vivo, or knock-down of Fe65 in neuroblastoma cells, was sufficient to abrogate normal GD3S functionality. Equally, knock-out of the presenilin genes, presenilin 1 and presenilin 2, essential for Aβ and AICD production, or of APP itself, increased GD3S activity and expression and consequently resulted in a major shift of a- to b-series gangliosides. In addition to GD3S regulation by APP processing, gangliosides in turn altered APP cleavage. GM3 decreased, whereas the ganglioside GD3, the GD3S product, increased Aβ production, resulting in a regulatory feedback cycle, directly linking ganglioside metabolism with APP processing and Aβ generation. A central aspect of this homeostatic control is the reduction of GD3S activity via an Aβ-GM3 complex and AICD

  14. Amyloid precursor protein (APP) mediated regulation of ganglioside homeostasis linking Alzheimer's disease pathology with ganglioside metabolism.

    PubMed

    Grimm, Marcus O W; Zinser, Eva G; Grösgen, Sven; Hundsdörfer, Benjamin; Rothhaar, Tatjana L; Burg, Verena K; Kaestner, Lars; Bayer, Thomas A; Lipp, Peter; Müller, Ulrike; Grimm, Heike S; Hartmann, Tobias

    2012-01-01

    Gangliosides are important players for controlling neuronal function and are directly involved in AD pathology. They are among the most potent stimulators of Aβ production, are enriched in amyloid plaques and bind amyloid beta (Aβ). However, the molecular mechanisms linking gangliosides with AD are unknown. Here we identified the previously unknown function of the amyloid precursor protein (APP), specifically its cleavage products Aβ and the APP intracellular domain (AICD), of regulating GD3-synthase (GD3S). Since GD3S is the key enzyme converting a- to b-series gangliosides, it therefore plays a major role in controlling the levels of major brain gangliosides. This regulation occurs by two separate and additive mechanisms. The first mechanism directly targets the enzymatic activity of GD3S: Upon binding of Aβ to the ganglioside GM3, the immediate substrate of the GD3S, enzymatic turnover of GM3 by GD3S was strongly reduced. The second mechanism targets GD3S expression. APP cleavage results, in addition to Aβ release, in the release of AICD, a known candidate for gene transcriptional regulation. AICD strongly down regulated GD3S transcription and knock-in of an AICD deletion mutant of APP in vivo, or knock-down of Fe65 in neuroblastoma cells, was sufficient to abrogate normal GD3S functionality. Equally, knock-out of the presenilin genes, presenilin 1 and presenilin 2, essential for Aβ and AICD production, or of APP itself, increased GD3S activity and expression and consequently resulted in a major shift of a- to b-series gangliosides. In addition to GD3S regulation by APP processing, gangliosides in turn altered APP cleavage. GM3 decreased, whereas the ganglioside GD3, the GD3S product, increased Aβ production, resulting in a regulatory feedback cycle, directly linking ganglioside metabolism with APP processing and Aβ generation. A central aspect of this homeostatic control is the reduction of GD3S activity via an Aβ-GM3 complex and AICD

  15. The S protein of bovine coronavirus is a hemagglutinin recognizing 9-O-acetylated sialic acid as a receptor determinant.

    PubMed Central

    Schultze, B; Gross, H J; Brossmer, R; Herrler, G

    1991-01-01

    The S protein of bovine coronavirus (BCV) has been isolated from the viral membrane and purified by gradient centrifugation. Purified S protein was identified as a viral hemagglutinin. Inactivation of the cellular receptors by sialate 9-O-acetylesterase and generation of receptors by sialylation of erythrocytes with N-acetyl-9-O-acetylneuraminic acid (Neu5,9Ac2) indicate that S protein recognizes 9-O-acetylated sialic acid as a receptor determinant as has been shown previously for intact virions. The second glycoprotein of BCV, HE, which has been thought previously to be responsible for the hemagglutinating activity of BCV, is a less efficient hemagglutinin; it agglutinates mouse and rat erythrocytes, but in contrast to S protein, it is unable to agglutinate chicken erythrocytes, which contain a lower level of Neu5,9Ac2 on their surface. S protein is proposed to be responsible for the primary attachment of virus to cell surface. S protein is proposed to be responsible for the primary attachement of virus to cell surface receptors. The potential of S protein as a probe for the detection of Neu5,9Ac2-containing glycoconjugates is demonstrated. Images PMID:1920630

  16. Synthesis of gangliosides by cultured oligodendrocytes

    SciTech Connect

    Mack, S.R.; Szuchet, S.; Dawson, G.

    1981-01-01

    Gangliosides are enriched in the nervous system compared to other tissues. The synthesis of gangliosides by monolayer cultures of isolated oligodendrocytes has not previously been investigated. Cells were labeled with (3H) galactose at preselected times and gangliosides isolated by phase partition, purified, and identified by chromatography. Cultured oligodendrocytes showed selectivity in their synthesis of gangliosides, which was expressed in the type of ganglioside synthesized as well as in the change of incorporation over time in culture. For the first ten days, there was very little incorporation of (3H) galactose in gangliosides, but this was followed by a stimulation of uptake for GM3, GM1/GD3, and GD1 gangliosides, reaching a maximum after approximately 25-30 days in vitro. There was little incorporation into GM2 or trisialogangliosides throughout the life of the cultures. Since oligodendrocytes synthesize extensive membranes during this period, one may speculate that the de novo-synthesized gangliosides are used for membranes.

  17. Modification of Ganglioside Content of Human Gastric Epithelial Cell Membrane Decreases Helicobacter pylori Adhesion.

    PubMed

    Rivas-Serna, Irma Magaly; Mazurak, Vera C; Keelan, Monika; Clandinin, Michael Thomas

    2017-10-01

    In polarized cells, ganglioside location determines ganglioside function. Diet alters ganglioside content and composition in cell membranes. Ganglioside acts as a receptor for Helicobacter pylori. H pylori infects the stomach epithelium and may cause peptic ulcer disease and gastric cancer. The present study used purified gangliosides to modify the ganglioside composition of human gastric epithelial cells in vitro to reduce H pylori adhesion. A human gastric epithelial cell line (NCI-N87) was cultured with a ganglioside mix or with pure ganglioside (GM3 or GD3) at different concentrations (0-30 μg/mL) and ganglioside membrane content of gastric cells was determined after 48 hours. LC/triple quadrupole MS was used to analyse ganglioside concentration. H pylori was inoculated into the culture media of gastric cells previously treated with gangliosides GM3 or GD3 or a combination of GM3 and GD3. GD3 and GM3 content increased in the plasma membrane in a dose-dependent manner. Gastric cells treated with GD3 showed more GM3 content than GD3 (P < 0.01). Ganglioside content was modified in the apical membrane, but GM3 and GD3 were also found in the basolateral membrane after treatments. Gastric cells treated with GM3, GD3 or the combination of GM3:GD3 decreased H pylori adhesion to gastric cells at all ganglioside concentrations tested by 80% compared with untreated gastric cells (P < 0.05). These observations suggest that GD3 and GM3 present in the stomach lumen may be taken up into the apical gastric membrane and decrease H pylori adhesion to the epithelium.

  18. Transfer of gangliosides across the human placenta.

    PubMed

    Mitchell, M D; Henare, K; Balakrishnan, B; Lowe, E; Fong, B Y; McJarrow, P

    2012-04-01

    Gangliosides are structural and functional glycosphingolipids, considered to have important roles in neuronal development in fetal and neonatal development and in memory formation. In this report, we have investigated the ability of bovine milk-derived gangliosides GM3 and GD3 to cross the human placenta. We have employed the ex-vivo model of dually-perfused isolated human placental lobules. There was significant uptake of both GD3 and GM3 from the maternal perfusate. There was significant increase of GM3 in the fetal side and a non-statistically significant trend for GD3 to increase on the fetal side. Hence an apparent preference for GM3 release into fetal circulation. We suggest that gangliosides consumed by the mother enter her circulation, can be transferred across the placenta and may be available to the developing fetus for building neural connections. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. [Gangliosides in the serum in lung carcinoma].

    PubMed

    Fumić, K; Vladović-Relja, T; Karada, J; Kracun, I; Stavljenić, A; Kubat, M; Cosović, C; Oberman, B

    1990-01-01

    In this study, tumor and serum gangliosides were analyzed in patients bearing lung planocellular carcinoma (LPC) before and after operative therapy. Tumor tissue, pathohistologically characterized as carcinoma planocellulare corneum (Ca. epidermoide, type 8070/3, WHO, Geneva, 1981), showed an elevated concentration of gangliosides in comparison to normal tung tissue. The composition of gangliosides in LPC tissue varied from one tumor sample to another, however, two general features were observed. First, LPC contained an increased amount of GM3 and a decreased amount of GD3 gangliosides. Second, an elevated proportion of gangliosides migrating as polysialogangliosides (x3, x5, x6) characterized the majority of LPC tissues. On the other hand, serum of patients with LPC contained an elevated amount of gangliosides (15.8 +/- 0.3 mumols/L) in comparison to control serum (6.1 +/- 0.8 mumols/L) (P less than 0.01). However, analyzing the composition of serum gangliosides by thin-layer chromatography, all serum gangliosides were more or less elevated. By day 21 after the surgical removal of LPC, serum gangliosides dropped by approximately 50% approaching the normal values. It seems that elevated serum gangliosides in LPC patients were secreted from carcinoma cells, because they normalized after surgical removal of LPC. Thus, serum gangliosides might be a useful biochemical tool for diagnosis and therapy monitoring of this carcinoma.

  20. Targeted deletion of GD3 synthase protects against MPTP-induced neurodegeneration.

    PubMed

    Akkhawattanangkul, Y; Maiti, P; Xue, Y; Aryal, D; Wetsel, W C; Hamilton, D; Fowler, S C; McDonald, M P

    2017-06-01

    Parkinson's disease is a debilitating neurodegenerative condition for which there is no cure. Converging evidence implicates gangliosides in the pathogenesis of several neurodegenerative diseases, suggesting a potential new class of therapeutic targets. We have shown that interventions that simultaneously increase the neuroprotective GM1 ganglioside and decrease the pro-apoptotic GD3 ganglioside - such as inhibition of GD3 synthase (GD3S) or administration of sialidase - are neuroprotective in vitro and in a number of preclinical models. In this study, we investigated the effects of GD3S deletion on parkinsonism induced by 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP was administered to GD3S-/- mice or controls using a subchronic regimen consisting of three series of low-dose injections (11 mg/kg/day × 5 days each, 3 weeks apart), and motor function was assessed after each. The typical battery of tests used to assess parkinsonism failed to detect deficits in MPTP-treated mice. More sensitive measures - such as the force-plate actimeter and treadmill gait parameters - detected subtle effects of MPTP, some of which were absent in mice lacking GD3S. In wild-type mice, MPTP destroyed 53% of the tyrosine-hydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNc) and reduced striatal dopamine 60.7%. In contrast, lesion size was only 22.5% in GD3S-/- mice and striatal dopamine was reduced by 37.2%. Stereological counts of Nissl-positive SNc neurons that did not express TH suggest that neuroprotection was complete but TH expression was suppressed in some cells. These results show that inhibition of GD3S has neuroprotective properties in the MPTP model and may warrant further investigation as a therapeutic target. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  1. Molecular identification of GD3 as a suppressor of the innate immune response in ovarian cancer

    PubMed Central

    Webb, Tonya J.; Li, Xiangming; Giuntoli, Robert L.; Lopez, Pablo H.H.; Heuser, Christoph; Schnaar, Ronald L.; Tsuji, Moriya; Kurts, Christian; Oelke, Mathias; Schneck, Jonathan P.

    2012-01-01

    Tumors often display mechanisms to avoid or suppress immune recognition. One such mechanism is the shedding of gangliosides into the local tumor microenvironment, and a high concentration of circulating gangliosides is associated with poor prognosis. In this study, we identify ganglioside GD3, which was isolated from the polar lipid fraction of ovarian cancer-associated ascites, as an inhibitory factor that prevents innate immune activation of natural killer T (NKT) cells. Purified GD3 displayed a high affinity for both human and mouse CD1d, a molecule involved in the presentation of lipid antigens to T cells. Purified GD3, as well as substances within the ascites, bound to the CD1d antigenic binding site and did not require additional processing for its inhibitory effect on NKT cells. Importantly, in vivo administration of GD3 inhibited α-GalCer- induced NKT cell activation in a dose dependent manner. These data therefore indicate that ovarian cancer tumors may use GD3 to inhibit the anti-tumor NKT cell response as an early mechanism of tumor immune evasion. PMID:22649190

  2. Neogenin, Defined as a GD3-associated Molecule by Enzyme-mediated Activation of Radical Sources, Confers Malignant Properties via Intracytoplasmic Domain in Melanoma Cells.

    PubMed

    Kaneko, Kei; Ohkawa, Yuki; Hashimoto, Noboru; Ohmi, Yuhsuke; Kotani, Norihiro; Honke, Koichi; Ogawa, Mitsutaka; Okajima, Tetsuya; Furukawa, Keiko; Furukawa, Koichi

    2016-08-05

    To investigate mechanisms for increased malignant properties in malignant melanomas by ganglioside GD3, enzyme-mediated activation of radical sources and subsequent mass spectrometry were performed using an anti-GD3 antibody and GD3-positive (GD3+) and GD3-negative (GD3-) melanoma cell lines. Neogenin, defined as a GD3-neighbored molecule, was largely localized in lipid/rafts in GD3+ cells. Silencing of neogenin resulted in the reduction of cell growth and invasion activity. Physical association between GD3 and neogenin was demonstrated by immunoblotting of the immunoprecipitates with anti-neogenin antibody from GD3+ cell lysates. The intracytoplasmic domain of neogenin (Ne-ICD) was detected in GD3+ cells at higher levels than in GD3- cells when cells were treated by a proteasome inhibitor but not when simultaneously treated with a γ-secretase inhibitor. Exogenous GD3 also induced increased Ne-ICD in GD3- cells. Overexpression of Ne-ICD in GD3- cells resulted in the increased cell growth and invasion activity, suggesting that Ne-ICD plays a role as a transcriptional factor to drive malignant properties of melanomas after cleavage with γ-secretase. γ-Secretase was found in lipid/rafts in GD3+ cells. Accordingly, immunocyto-staining revealed that GD3, neogenin, and γ-secretase were co-localized at the leading edge of GD3+ cells. All these results suggested that GD3 recruits γ-secretase to lipid/rafts, allowing efficient cleavage of neogenin. ChIP-sequencing was performed to identify candidates of target genes of Ne-ICD. Some of them actually showed increased expression after expression of Ne-ICD, probably exerting malignant phenotypes of melanomas under GD3 expression. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Oncotargets GD2 and GD3 are highly expressed in sarcomas of children, adolescents, and young adults.

    PubMed

    Dobrenkov, Konstantin; Ostrovnaya, Irina; Gu, Jessie; Cheung, Irene Y; Cheung, Nai-Kong V

    2016-10-01

    GD2 and GD3 are the tumor-associated glycolipid antigens found in a broad spectrum of human cancers. GD2-specific antibody is currently a standard of care for high-risk neuroblastoma therapy. In this study, the pattern of GD2 and GD3 expression among pediatric/adolescent or young adult tumors was determined, providing companion diagnostics for targeted therapy. Ninety-two specimens of human osteosarcoma (OS), rhabdomyosarcoma (RMS), Ewing family of tumors, desmoplastic small round cell tumor (DSRCT), and melanoma were analyzed for GD2/GD3 expression by immunohistochemistry. Murine monoclonal antibody 3F8 was used for GD2 staining, and R24 for GD3. Staining was scored according to both intensity and percentage of positive tumor cells from 0 to 4. Both gangliosides were highly prevalent in OS and melanoma. Among other tumors, GD3 expression was higher than GD2 expression. Most OS samples demonstrated strong staining for GD2 and GD3, whereas expression for other tumors was highly variable. Mean intensity of GD2 expression was significantly more heterogeneous (P < 0.001) when compared to GD3 across tumor types. When assessing the difference between GD2 and GD3 expression in all tumor types combined, GD3 expression had a significantly higher score (P = 0.049). When analyzed within each cancer, GD3 expression was significantly higher only in DSRCT (P = 0.002). There was no statistical difference in either GD2 or GD3 expression between primary and recurrent sarcomas. GD2/GD3 expression among pediatric solid tumors is common, albeit with variable level of expression. Especially for patients with sarcoma, these gangliosides can be potential targets for antibody-based therapies. © 2016 Wiley Periodicals, Inc.

  4. Ganglioside glycosyltransferases and newly synthesized gangliosides are excluded from detergent-insoluble complexes of Golgi membranes.

    PubMed

    Crespo, Pilar M; Zurita, Adolfo R; Giraudo, Claudio G; Maccioni, Hugo J F; Daniotti, Jose L

    2004-02-01

    GEM (glycosphingolipid-enriched microdomains) are specialized detergent-resistant domains of the plasma membrane in which some gangliosides concentrate. Although genesis of GEM is considered to occur in the Golgi complex, where the synthesis of gangliosides also occurs, the issue concerning the incorporation of ganglioside species into GEM is still poorly understood. In this work, using Chinese hamster ovary K1 cell clones with different glycolipid compositions, we compared the behaviour with cold Triton X-100 solubilization of plasma membrane ganglioside species with the same species newly synthesized in Golgi membranes. We also investigated whether three ganglioside glycosyltransferases (a sialyl-, a N-acetylgalactosaminyl- and a galactosyl-transferase) are included or excluded from GEM in Golgi membranes. Our data show that an important fraction of plasma membrane G(M3), and most G(D3) and G(T3), reside in GEM. Immunocytochemical examination of G(D3)-expressing cells showed G(D3) to be distributed as cold-detergent-resistant patches in the plasma membrane. These patches did not co-localize with a glycosylphosphatidylinositol-anchored protein used as GEM marker, indicating a heterogeneous composition of plasma membrane GEM. In Golgi membranes we were unable to find evidence for GEM localization of either ganglioside glycosyltransferases or newly synthesized gangliosides. Since the same ganglioside species appear in plasma membrane GEM, it was concluded that in vivo nascent G(D3), G(T3) and G(M3) segregate from their synthesizing transferases and then enter GEM. This latter event could have taken place shortly after synthesis in the Golgi cisternae, along the secretory pathway and/or at the cell surface.

  5. Structural characterization of gangliosides isolated from mullet milt using electrospray ionization-tandem mass spectrometry.

    PubMed

    Zhu, J; Li, Y T; Li, S C; Cole, R B

    1999-10-01

    Electrospray ionization (ESI) coupled with tandem mass spectrometry has been used in conjunction with microwave-mediated saponification, periodate oxidation, and clostridial sialidase hydrolysis to enable detailed structural characterization of gangliosides and their derivatives present in mullet milt. The gangliosides extracted from mullet milt were determined to be GM3, GM3 lactone, GM3 methyl ester, and 9-O-acetyl GM3. For the major ganglioside GM3 and all GM3 derivatives, the ceramide composition was revealed to be C18:1/C16:0. GM3 with a C18:0/C16:0 ceramide was also found as a minor ganglioside. Both the ganglioside intramolecular ester and the ganglioside methyl ester (lacking carboxylic acid groups) showed dominant chloride attachment peaks (M + Cl)- in negative ion ESI-MS in addition to low intensity peaks corresponding to (M-H)-. GM3 and O-acetyl GM3 bearing carboxylic acid functions showed only (M-H)-. In positive ion ESI, GM3 and O-acetyl GM3 revealed (M + 2Na-H)+ peaks in addition to (M + Na)+, indicating free exchange of the carboxylic acid proton with a sodium cation, while the ganglioside intramolecular ester and ganglioside methyl ester with no acidic protons yielded only (M + Na)+. The strategy of employing ESI-MS to detect products of established wet chemical reactions represents a general approach for elucidation of ganglioside structural details.

  6. Regulation by GD3 of the proinflammatory response of microglia mediated by interleukin-15.

    PubMed

    Gómez-Nicola, Diego; Doncel-Pérez, Ernesto; Nieto-Sampedro, Manuel

    2006-04-01

    The interleukin (IL)-15-dependent immune responses of murine microglia were strongly affected by low concentrations of the ganglioside GD3. The ganglioside binding to IL-15 inhibited the proinflammatory effects of the cytokine, reducing IL-15-dependent T-cell proliferation as well as mRNA expression for IL-15Ralpha, p65, and NFATc2 in the N13 murine microglial cell line. Treatment of primary murine microglial cultures with GD3 abolished IL-15 production, without affecting cellular viability, but decreased the production of nitric oxide, a direct sensor of inflammation and nuclear factor-kappaB activity. We conclude that low doses of GD3 could inhibit specific proinflammatory mechanisms and modulate the inflammatory environment, leading to a less reactive scene. Microglial cells are one of the main actors in the inflammatory events that follow CNS trauma or an autoimmune disease episode, modulating the internal production of cytokines, growth factors, and other homeostatic molecules that may determine the evolution and outcome of tissue damage. Proinflammatory cytokines have a relevant role in the initial events, and modulation of their activity by gangliosides could cut down their harmful effects and interfere with invasion of the CNS by peripheral immune cells. The antiinflammatory properties of GD3 could be significant in the treatment of pain subsequent to CNS damage.

  7. Ganglioside binding pattern of CD33-related siglecs.

    PubMed

    Rapoport, Eugenia; Mikhalyov, Ilya; Zhang, Jiquan; Crocker, Paul; Bovin, Nicolai

    2003-02-24

    Our study deals with the interaction of CD33 related-siglecs-5,-7,-8,-9,-10 with gangliosides GT1b, GQ1b, GD3, GM2, GM3 and GD1a. Siglec-5 bound preferentially to GQ1b, but weakly to GT1b, whereas siglec-10 interacted only with GT1b ganglioside. Siglec-7 and siglec-9 displayed binding to gangliosides GD3, GQ1b and GT1b bearing a disialoside motif, though siglec-7 was more potent; besides, siglec-9 interacted also with GM3. Siglec-8 demonstrated low affinity to the gangliosides tested compared with other siglecs. Despite high structural similarity of CD33 related siglecs, they demonstrated different ganglioside selectivity, in particular to the Neu5Acalpha2-8Neu5Ac motif.

  8. Identification of N-acetylneuraminic acid and its 9-O-acetylated derivative on the cell surface of Cryptococcus neoformans: influence on fungal phagocytosis.

    PubMed Central

    Rodrigues, M L; Rozental, S; Couceiro, J N; Angluster, J; Alviano, C S; Travassos, L R

    1997-01-01

    Sialic acids from sialoglycoconjugates present at the cell surface of Cryptococcus neoformans yeast forms were analyzed by high-performance thin-layer chromatography, binding of influenza A and C virus strains, enzymatic treatment, and flow cytofluorimetry with fluorescein isothiocyanate-labeled lectins. C. neoformans yeast forms grown in a chemically defined medium contain N-acetylneuraminic acid and its 9-O-acetylated derivative. A density of 3 x 10(6) residues of sialic acid per cell was found in C. neoformans. Sialic acids in cryptococcal cells are glycosidically linked to galactopyranosyl units as inferred from the increased reactivity of neuraminidase-treated yeasts with peanut agglutinin. N-Acetylneuraminic acids are alpha-2,6 and alpha-2,3 linked, as indicated by using virus strains M1/5 and M1/5 HS8, respectively, as agglutination probes. The alpha-2,6 linkage markedly predominated. These findings were essentially confirmed by the interaction of cryptococcal cells with the lectins Sambucus nigra agglutinin and Maackia amurensis agglutinin. We also investigated whether the sialyl residues present in C. neoformans are involved in the fungal interaction with a cationic solid-phase substrate and with mouse resident macrophages. Adhesion of yeast cells to poly-L-lysine was mediated, in part, by sialic acid residues, since the number of adherent cells was markedly reduced after treatment with bacterial neuraminidase. The enzymatic removal of sialic acids also made C. neoformans yeast cells more susceptible to endocytosis by macrophages. The results show that sialic acids are components of the cryptococcal cell surface that contribute to its negative charge and protect yeast forms against phagocytosis. PMID:9393779

  9. The sialate O-acetylesterase EstA from gut Bacteroidetes species enables sialidase-mediated cross-species foraging of 9-O-acetylated sialoglycans.

    PubMed

    Robinson, Lloyd S; Lewis, Warren G; Lewis, Amanda L

    2017-07-14

    The gut harbors many symbiotic, commensal, and pathogenic microbes that break down and metabolize host carbohydrates. Sialic acids are prominent outermost carbohydrates on host glycoproteins called mucins and protect underlying glycan chains from enzymatic degradation. Sialidases produced by some members of the colonic microbiota can promote the expansion of several potential pathogens (e.g. Clostridium difficile, Salmonella, and Escherichia coli) that do not produce sialidases. O-Acetyl ester modifications of sialic acids help resist the action of many sialidases and are present at high levels in the mammalian colon. However, some gut bacteria, in turn, produce sialylate-O-acetylesterases to remove them. Here, we investigated O-acetyl ester removal and sialic acid degradation by Bacteroidetes sialate-O-acetylesterases and sialidases, respectively, and subsequent utilization of host sialic acids by both commensal and pathogenic E. coli strains. In vitro foraging studies demonstrated that sialidase-dependent E. coli growth on mucin is enabled by Bacteroides EstA, a sialate O-acetylesterase acting on glycosidically linked sialylate-O-acetylesterase substrates, particularly at neutral pH. Biochemical studies suggested that spontaneous migration of O-acetyl esters on the sialic acid side chain, which can occur at colonic pH, may serve as a switch controlling EstA-assisted sialic acid liberation. Specifically, EstA did not act on O-acetyl esters in their initial 7-position. However, following migration to the 9-position, glycans with O-acetyl esters became susceptible to the sequential actions of bacterial esterases and sialidases. We conclude that EstA specifically unlocks the nutritive potential of 9-O-acetylated mucus sialic acids for foraging by bacteria that otherwise are prevented from accessing this carbon source. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. The sialate O-acetylesterase EstA from gut Bacteroidetes species enables sialidase-mediated cross-species foraging of 9-O-acetylated sialoglycans

    PubMed Central

    Robinson, Lloyd S.; Lewis, Warren G.

    2017-01-01

    The gut harbors many symbiotic, commensal, and pathogenic microbes that break down and metabolize host carbohydrates. Sialic acids are prominent outermost carbohydrates on host glycoproteins called mucins and protect underlying glycan chains from enzymatic degradation. Sialidases produced by some members of the colonic microbiota can promote the expansion of several potential pathogens (e.g. Clostridium difficile, Salmonella, and Escherichia coli) that do not produce sialidases. O-Acetyl ester modifications of sialic acids help resist the action of many sialidases and are present at high levels in the mammalian colon. However, some gut bacteria, in turn, produce sialylate-O-acetylesterases to remove them. Here, we investigated O-acetyl ester removal and sialic acid degradation by Bacteroidetes sialate-O-acetylesterases and sialidases, respectively, and subsequent utilization of host sialic acids by both commensal and pathogenic E. coli strains. In vitro foraging studies demonstrated that sialidase-dependent E. coli growth on mucin is enabled by Bacteroides EstA, a sialate O-acetylesterase acting on glycosidically linked sialylate-O-acetylesterase substrates, particularly at neutral pH. Biochemical studies suggested that spontaneous migration of O-acetyl esters on the sialic acid side chain, which can occur at colonic pH, may serve as a switch controlling EstA-assisted sialic acid liberation. Specifically, EstA did not act on O-acetyl esters in their initial 7-position. However, following migration to the 9-position, glycans with O-acetyl esters became susceptible to the sequential actions of bacterial esterases and sialidases. We conclude that EstA specifically unlocks the nutritive potential of 9-O-acetylated mucus sialic acids for foraging by bacteria that otherwise are prevented from accessing this carbon source. PMID:28526748

  11. Studies on the biosynthesis and intracellular transport of gangliosides

    SciTech Connect

    Farrer, R.G.

    1987-01-01

    Ganglioside biosynthesis and transport to myelin was studied in brainstem of 17-21 day old rats. Brainstem slices were incubated for up to 2 hours with (/sup 3/H)glucosamine, and gangliosides were isolated by column chromatography and HPTLC. Results from these experiments showed that: (a) ganglioside synthesis was decreased in the slices compared to in vivo, and this decrease was greater in the more complex gangliosides than in the simpler ones; (b) label incorporation into gangliosides GM3 and GM2 increased in a linear fashion, whereas the rate of incorporation continuously increased over the 2 hour period for the more complex gangliosides; (c) label incorporated into gangliosides, which showed almost no effect of chase after 30 minutes; (d) monensin at 0.1 uM inhibited the synthesis of all gangliosides except GM3, GM2 and GD3. Compartmentation of ganglioside biosynthesis was examined by analyzing the subcellular location of two ganglioside synthesizing enzymes, lactosylceramide sialosyltransferase (LCST) and GDlb sialosyltransferase (GDlbST), acting early and late in the ganglioside pathway, respectively.

  12. O-acetylated sialic acids in gangliosides from pig spleen lymphocytes.

    PubMed

    Hueso, P; Cabezas, J A; Reglero, A

    1988-01-01

    The sialic acid content of gangliosides from pig spleen lymphocytes was studied by thin-layer chromatography. N-glycolylneuraminic acid and N-acetylneuraminic acid were detected for the first time in this material as the major sialic acids. In addition, two other sialic acids, tentatively designated O-acetylated sialic acids, according to their RF values on cellulose plates, were also found. We have detected several gangliosides showing a retarded migration pattern in two dimensional thin-layer chromatography with an intermediate ammonia treatment. One of these gangliosides could be an O-acetylated derivative of the disialoganglioside GD3, since after de-O-acetyation it co-migrates with GD3. Another ganglioside co-migrated with GM2 before the alkaline treatment; however, after the treatment it was also retarded and co-migrates with GD3.

  13. Complex gangliosides are apically sorted in polarized MDCK cells and internalized by clathrin-independent endocytosis.

    PubMed

    Crespo, Pilar M; von Muhlinen, Natalia; Iglesias-Bartolomé, Ramiro; Daniotti, Jose L

    2008-12-01

    Gangliosides are glycosphingolipids mainly present at the outer leaflet of the plasma membrane of eukaryotic cells, where they participate in recognition and signalling activities. The synthesis of gangliosides is carried out in the lumen of the Golgi apparatus by a complex system of glycosyltransferases. After synthesis, gangliosides leave the Golgi apparatus via the lumenal surface of transport vesicles destined to the plasma membrane. In this study, we analysed the synthesis and membrane distribution of GD3 and GM1 gangliosides endogenously synthesized by Madin-Darby canine kidney (MDCK) cell lines genetically modified to express appropriate ganglioside glycosyltransferases. Using biochemical techniques and confocal laser scanning microscopy analysis, we demonstrated that GD3 and GM1, after being synthesized at the Golgi apparatus, were transported and accumulated mainly at the plasma membrane of nonpolarized MDCK cell lines. More interestingly, both complex gangliosides were found to be enriched mainly at the apical domain when these cell lines were induced to polarize. In addition, we demonstrated that, after arrival at the plasma membrane, GD3 and GM1 gangliosides were endocytosed using a clathrin-independent pathway. Then, internalized GD3, in association with a specific monoclonal antibody, was accumulated in endosomal compartments and transported back to the plasma membrane. In contrast, endocytosed GM1, in association with cholera toxin, was transported to endosomal compartments en route to the Golgi apparatus. In conclusion, our results demonstrate that complex gangliosides are apically sorted in polarized MDCK cells, and that GD3 and GM1 gangliosides are internalized by clathrin-independent endocytosis to follow different intracellular destinations.

  14. Ganglioside Biochemistry

    PubMed Central

    Kolter, Thomas

    2012-01-01

    Gangliosides are sialic acid-containing glycosphingolipids. They occur especially on the cellular surfaces of neuronal cells, where they form a complex pattern, but are also found in many other cell types. The paper provides a general overview on their structures, occurrence, and metabolism. Key functional, biochemical, and pathobiochemical aspects are summarized. PMID:25969757

  15. Time domain simulation of Gd3+-Gd3+ distance measurements by EPR

    NASA Astrophysics Data System (ADS)

    Manukovsky, Nurit; Feintuch, Akiva; Kuprov, Ilya; Goldfarb, Daniella

    2017-07-01

    Gd3+-based spin labels are useful as an alternative to nitroxides for intramolecular distance measurements at high fields in biological systems. However, double electron-electron resonance (DEER) measurements using model Gd3+ complexes featured a low modulation depth and an unexpected broadening of the distance distribution for short Gd3+-Gd3+ distances, when analysed using the software designed for S = 1/2 pairs. It appears that these effects result from the different spectroscopic characteristics of Gd3+—the high spin, the zero field splitting (ZFS), and the flip-flop terms in the dipolar Hamiltonian that are often ignored for spin-1/2 systems. An understanding of the factors affecting the modulation frequency and amplitude is essential for the correct analysis of Gd3+-Gd3+ DEER data and for the educated choice of experimental settings, such as Gd3+ spin label type and the pulse parameters. This work uses time-domain simulations of Gd3+-Gd3+ DEER by explicit density matrix propagation to elucidate the factors shaping Gd3+ DEER traces. The simulations show that mixing between the |+½, -½> and |-½, +½> states of the two spins, caused by the flip-flop term in the dipolar Hamiltonian, leads to dampening of the dipolar modulation. This effect may be mitigated by a large ZFS or by pulse frequency settings allowing for a decreased contribution of the central transition and the one adjacent to it. The simulations reproduce both the experimental line shapes of the Fourier-transforms of the DEER time domain traces and the trends in the behaviour of the modulation depth, thus enabling a more systematic design and analysis of Gd3+ DEER experiments.

  16. Characterization and chronological changes of preterm human milk gangliosides.

    PubMed

    Uchiyama, Shin-ichi; Sekiguchi, Kazuhito; Akaishi, Mutsumi; Anan, Aki; Maeda, Tomoki; Izumi, Tatsuro

    2011-10-01

    Gangliosides are present in high concentrations in the nervous tissue, and some are observed in small amounts in many extraneural tissues and body fluids. Human milk may play important roles in energy supplementation, prophylaxis of infection, and brain development. For preterm infants, human milk gangliosides are also very important substances during the early lactation stage. However, there are no data on human milk gangliosides from mothers at preterm delivery. We investigated the characterization of gangliosides and chronologic changes in human preterm milk earlier than 30 wk of gestation from 1 to 60 d after birth. Forty-one samples were analyzed by high-performance thin-layer chromatography and a microtechnique using 1 mL of milk from each lactation and compared with 61 full-term human milk samples. Total lipid-bound sialic acid of human milk gangliosides after preterm delivery showed a peak concentration at 2 to 3 d postpartum and then remained at a high concentration until approximately 10 d. GD3 was the major ganglioside in the colostrum until approximately 7 to 10 d postpartum. GM3 was scarcely detected until 7 d postpartum and then increased gradually. There was no difference in the GD3 concentration per 1 mL of human milk between preterm and full-term human milk until approximately 5 to 8 d postpartum. After that time, the GD3 concentration decreased sharply. In contrast, the total concentrations of GM3 per 1 mL of human milk from mothers after preterm delivery were lower than those from mothers after full-term delivery throughout the entire period examined. This finding is essential to elucidate the composition of human milk gangliosides after preterm delivery, which may contribute to the analysis of the physiologic composition and formulation appropriate preterm infant nutrition. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. The role of 9-O-acetylated ganglioside D3 (CD60) and α4β1 (CD49d) expression in predicting the survival of patients with Sézary syndrome

    PubMed Central

    Scala, Enrico; Abeni, Damiano; Pomponi, Debora; Narducci, Maria Grazia; Lombardo, Giuseppe Alfonso; Mari, Adriano; Frontani, Marina; Picchio, Maria Cristina; Pilla, Maria Antonietta; Caprini, Elisabetta; Russo, Giandomenico

    2010-01-01

    Background Sézary syndrome is a rare and very aggressive leukemic variant of cutaneous T-cell lymphoma characterized by extensive skin involvement and a malignant circulating CD4+ T-cell clone which homes to the skin, over-expresses CD60, and lacks CD7, CD26 and CD49d. So far prognostic markers in this disease are limited to treatment with systemic steroids, age, serum lactate dehydrogenase, and a white blood cell count of 20×109/L or higher: no other biological marker with prognostic value, especially related to malignant cells, has been described. Design and Methods We used flow activated cell sorting analysis to compare the distribution of the T-cell receptor-Vβ repertoire and several surface molecules (CD7, CD26, CD49d and CD60) within the circulating CD4+ T-cell population in 62 patients with Sézary syndrome, 180 with mycosis fungoides, 6 with B-cell lymphomas, and 19 with chronic eczema. We calculated the 5-year overall survival of patients with Sézary syndrome after first hospital admission using Kaplan–Meier product–limit estimates and hazard ratios from the Cox proportional hazards model. Results We found that both higher number of CD60+ and lower number of CD49d+ cells within circulating CD4+ T cells at disease presentation were significantly associated with a lower probability of survival. An exceedingly high risk of death was observed for patients with a combination of a high proportion of CD4+CD60+ cells (≥ 0.5×109/L) and low proportion of CD4+CD49d+ cells (<0.5×109/L) (hazard ratio = 12.303, 95% confidence interval 1.5–95.9; P<0.02). In addition, a skewed usage of T-cell receptor-Vβ subfamilies was observed in the circulating T-cell clone for 61.9% of all patients with Sézary syndrome, T-cell receptor-Vβ 2 and 5.1 subfamilies being the most frequently represented (42.8%), followed by T-cell receptor-Vβ 12 and 13.1. Conclusions In this study we showed that up-regulation of CD60 and down-regulation of CD49d on circulating CD4+ T cells are two useful markers for predicting a very poor outcome in patients with Sézary syndrome. PMID:20663947

  18. Different mechanisms are involved in apoptosis induced by melanoma gangliosides on human monocyte-derived dendritic cells.

    PubMed

    Bennaceur, Karim; Popa, Iuliana; Chapman, Jessica Alice; Migdal, Camille; Péguet-Navarro, Josette; Touraine, Jean-Louis; Portoukalian, Jacques

    2009-06-01

    Tumor escape is linked to multiple mechanisms, notably the liberation, by tumor cells, of soluble factors that inhibit the function of dendritic cells (DC). We have shown that melanoma gangliosides impair DC differentiation and induce their apoptosis. The present study was aimed to give insight into the mechanisms involved. DC apoptosis was independent of the catabolism of gangliosides since lactosylceramide did not induce cell death. Apoptosis induced by GM3 and GD3 gangliosides was not blocked by inhibitors of de novo ceramide biosynthesis, whereas the acid sphingomyelinase inhibitor desipramine only prevented apoptosis induced by GM3. Furthermore, our results suggest that DC apoptosis was triggered via caspase activation, and it was ROS dependent with GD3 ganglioside, suggesting that GM3 and GD3 induced apoptosis through different mechanisms.

  19. Different mechanisms are involved in apoptosis induced by melanoma gangliosides on human monocyte-derived dendritic cells

    PubMed Central

    Bennaceur, Karim; Popa, Iuliana; Chapman, Jessica Alice; Migdal, Camille; Péguet-Navarro, Josette; Touraine, Jean-Louis; Portoukalian, Jacques

    2009-01-01

    Tumor escape is linked to multiple mechanisms, notably the liberation, by tumor cells, of soluble factors that inhibit the function of dendritic cells (DC). We have shown that melanoma gangliosides impair DC differentiation and induce their apoptosis. The present study was aimed to give insight into the mechanisms involved. DC apoptosis was independent of the catabolism of gangliosides since lactosylceramide did not induce cell death. Apoptosis induced by GM3 and GD3 gangliosides was not blocked by inhibitors of de novo ceramide biosynthesis, whereas the acid sphingomyelinase inhibitor desipramine only prevented apoptosis induced by GM3. Furthermore, our results suggest that DC apoptosis was triggered via caspase activation, and it was ROS dependent with GD3 ganglioside, suggesting that GM3 and GD3 induced apoptosis through different mechanisms. PMID:19240275

  20. Effect of Dietary Complex Lipids on the Biosynthesis of Piglet Brain Gangliosides.

    PubMed

    Reis, Marlon M; Bermingham, Emma N; Reis, Mariza G; Deb-Choudhury, Santanu; MacGibbon, Alastair; Fong, Bertram; McJarrow, Paul; Bibiloni, Rodrigo; Bassett, Shalome A; Roy, Nicole C

    2016-02-17

    Gangliosides, found in mammalian milk, are known for their roles in brain development of the newborn. However, the mechanism involved in the impact of dietary gangliosides on brain metabolism is not fully understood. The impact of diets containing complex lipids rich in milk-derived ganglioside GD3 on the biosynthesis of gangliosides (assessed from the incorporation of deuterium) in the frontal lobe of a piglet model is reported. Higher levels of incorporation of deuterium was observed in the GM1 and GD1a containing stearic acid in samples from piglets fed milk containing 18.2 μg/mL of GD3 compared to that in those fed milk containing 25 μg/mL of GD3. This could suggest that the gangliosides from the diet may be used as a precursor for de novo biosynthesis of brain gangliosides or lead to the reduction of de novo biosynthesis of these gangliosides. This effect was more pronounced in the left compared to that in the right brain hemisphere.

  1. Aberrant ganglioside composition in glioblastoma multiforme and peritumoral tissue: A mass spectrometry characterization.

    PubMed

    Fabris, Dragana; Rožman, Marko; Sajko, Tomislav; Vukelić, Željka

    2017-06-01

    Tumor cells are characterized by aberrant glycosylation of the cell surface glycoconjugates. Gangliosides are sialylated glycosphingolipids highly abundant in neural tissue and considered as tumor markers and therapeutic targets. In this study, a detailed characterization of native ganglioside mixtures from glioblastoma multiforme, corresponding peritumoral tissue and healthy human brain was performed using mass spectrometry and high performance thin layer chromatography in order to elucidate their roles as tumor-associated antigens. Distinctive changes in ganglioside expression were determined in glioblastoma compared to healthy brain tissue showing 5 times lower total ganglioside content and higher abundance of simple gangliosides. Glioblastoma gangliosides were characterized by highly diverse ceramide composition with fatty acyl chains varying from 16 to 24 carbon atoms, while in normal and peritumoral tissue mostly C18 chains were found. The most abundant ganglioside in glioblastoma was GD3 (d18:1/18:0), followed by GD3 (d18:1/24:0) that was exclusively detected in glioblastoma tissue. Peritumoral tissue expressed higher abundance of GD3- and nLM1/GM1-species while lower GT1-species vs. normal brain. O-Ac-GD1, known as neurostatin, was detected in normal and peritumoral tissue, but not in glioblastoma. O-Ac-GD3 species were found exclusively in glioblastoma; MS structural characterization of the isomeric form possessing the O-acetylation at the inner sialic acid residue confirmed our previous finding that this isomer is glioma-associated. This, to our knowledge, the most detailed characterization of ganglioside composition in glioblastoma and peritumoral tissue, especially addressing the ceramide variability and O-acetylation of tumor-associated gangliosides, could contribute to recognition of new molecular targets for glioblastoma treatment and sub-classification. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Mol

  2. Neuroprotective Ganglioside Derivatives

    DTIC Science & Technology

    2002-09-01

    In this study, neuroprotective ganglioside derivatives are examined so they can be targeted to specific points in cell death pathways. GM1... ganglioside and several of its chemically modified derivatives are neuroprotective in several neurotoxic models. Here, ganglioside functional groups required... ganglioside derivatives intervene in the cell death process. In the first year, substantial quantities of GM1 have been isolated and purified.

  3. Plasmatic Ganglioside Profile and Age-Related Macular Degeneration: A Case-Control Study.

    PubMed

    Dossarps, Denis; Martine, Lucy; Berdeaux, Olivier; Sibille, Estelle; Bron, Alain M; Creuzot-Garcher, Catherine P; Bretillon, Lionel; Masson, Elodie A Y

    2016-01-01

    Gangliosides are glycosphingolipids that are particularly abundant in the nervous system, including the retina. However, their precise role in this tissue and its pathologies remain poorly understood. The objective of the present study was to characterize the ganglioside profile of human plasma and to determine whether it is affected in age-related macular degeneration (AMD). Eighty-three subjects were included: control subjects (n = 25), atrophic AMD patients (n = 27) and exudative AMD patients (n = 31). For each subject, gangliosides were extracted from plasma and analyzed by liquid chromatography coupled to mass spectrometry. GM3 appeared to be by far the major ganglioside of human plasma, associated with GD3. No specific ganglioside class was detected in the plasma of AMD patients. Fourteen molecular species of GM3 and 9 species of GD3, accounting for the variability of the ceramide moiety of the ganglioside molecule, were identified and characterized. Analyses revealed no significant differences in the proportion of these species between control, atrophic and exudative AMD patient groups. Total GM3 levels did not differ either. Although gangliosides are considered important for the retina's structure and function, it seems that circulating gangliosides are not associated with the retinal damage occurring during the course of AMD. © 2016 S. Karger AG, Basel.

  4. Determination of disialoganglioside GD3 and monosialoganglioside GM3 in infant formulas and whey protein concentrates by ultra-performance liquid chromatography/electrospray ionization tandem mass spectrometry.

    PubMed

    Zhang, Jingshun; Ren, Yiping; Huang, Baifen; Tao, Baohua; Pedersen, Marlene Ransborg; Li, Duo

    2012-04-01

    A method of ultra-performance liquid chromatography combined with electrospray ionization triple quadrupole tandem mass spectrometry (UPLC-ESI-MS/MS) has been established for simultaneous determination of major disialoganglioside 3 (GD3) and monosialoganglioside 3 (GM3) in infant formulas and whey protein concentrates. Gangliosides were extracted by using the technique of Svennerholm and Fredman and then cleaned up with OASIS HLB solid-phase extraction (SPE) cartridges. The various molecular species of gangliosides were separated on an Acquity UPLC BEH C8 column and analyzed under the negative ion mode. GD3 and GM3 were rapidly quantified using internal standard (IS) method. The developed method was further validated by determining the linearity, average recovery, sensitivity (limit of quantification), and precision. The results presented high correlation coefficients (R(2) > 0.993) of the selected 16 gangliosides molecular species and provided the respective linear ranges. The limit of quantification was 0.325-0.734 mg/100 g for eight molecular species of GD3 and 0.008-0.312 mg/100 g for eight molecular species of GM3, respectively. The reasonable average recoveries (81-95%) and precision (relative standard deviation [RSD] ≤15%) were also demonstrated in three different spiked levels. This new method would be very useful in the quantitative determination of gangliosides in infant formulas and whey protein concentrates. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Alterations of membrane lipids and in gene expression of ganglioside metabolism in different brain structures in a mouse model of mucopolysaccharidosis type I (MPS I).

    PubMed

    Kreutz, Fernando; dos Santos Petry, Fernanda; Camassola, Melissa; Schein, Vanessa; Guma, Fátima C R; Nardi, Nance Beyer; Trindade, Vera Maria Treis

    2013-09-15

    Mucopolysaccharidosis I (MPS I) is a congenital disorder caused by the deficiency of α-l-iduronidase (IDUA), with the accumulation of glycosaminoglycans (GAGs) in the CNS. Although GAG toxicity is not fully understood, previous works suggest a GAG-induced alteration in neuronal membrane composition. This study is aimed to evaluate the levels and distribution of gangliosides and cholesterol in different brain regions (cortex, cerebellum, hippocampus and hypothalamus) in a model using IDUA knockout (KO) mice (C57BL/6). Lipids were extracted with chloroform-methanol and then total gangliosides and cholesterol were determined, followed by ganglioside profile analyses. While no changes in cholesterol content were observed, the results showed a tissue dependent ganglioside alteration in KO mice: a total ganglioside increase in cortex and cerebellum, and a selective presence of GM3, GM2 and GD3 gangliosides in the hippocampus and hypothalamus. To elucidate this, we evaluated gene expression of ganglioside synthesis (GM3, GD3 and GM2/GD2 synthases) and degradation of (Neuraminidase1) enzymes in the cerebellum and hippocampus by RT-sq-PCR. The results obtained with KO mice showed a reduced expression of GD3 and GM2/GD2 synthases and Neuraminidase1 in cerebellum; and a decrease in GM2/GD2 synthase and Neuraminidase1 in the hippocampus. These data suggest that the observed ganglioside changes result from a combined effect of GAGs on ganglioside biosynthesis and degradation. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Hydrolysis of milk gangliosides by infant-gut associated bifidobacteria determined by microfluidic chips and high-resolution mass spectrometry.

    PubMed

    Lee, Hyeyoung; Garrido, Daniel; Mills, David A; Barile, Daniela

    2014-06-01

    Gangliosides are receiving considerable attention because they participate in diverse biological processes. Milk gangliosides appear to block pathogen adhesion and modify the intestinal ecology of newborns. However, the interaction of milk gangliosides with gut bifidobacteria has been little investigated. The digestion products of a mixture of gangliosides isolated from milk following incubation with six strains of bifidobacteria were studied using nanoHPLC Chip Q-TOF MS. To understand ganglioside catabolism in vitro, the two major milk gangliosides--GM3 and GD3--remaining in the media after incubation with bifidobacteria were quantified. Individual gangliosides were identified through postprocessing precursor ion scans, and quantitated with the "find by molecular feature" algorithm of MassHunter Qualitative Analysis software. Bifidobacterium infantis and B. bifidum substantially degraded the GM3 and GD3, whereas B. longum subsp. longum and B. animalis subsp. lactis only showed moderate degradation. MALDI FTICR MS analysis enabled a deeper investigation of the degradation and identified ganglioside degradation specifically at the outer portions of the glycan molecules. These results indicate that certain infant gut-associated bifidobacteria have the ability to degrade milk gangliosides releasing sialic acid, and that these glycolipids could play a prebiotic role in the infant gut. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Production of Multiple Brain-Like Ganglioside Species Is Dispensable for Fas-Induced Apoptosis of Lymphoid Cells

    PubMed Central

    Carpentier, Stéphane; Levade, Thierry; Cuvillier, Olivier; Portoukalian, Jacques

    2011-01-01

    Activation of an acid sphingomyelinase (aSMase) leading to a biosynthesis of GD3 disialoganglioside has been associated with Fas-induced apoptosis of lymphoid cells. The present study was undertaken to clarify the role of this enzyme in the generation of gangliosides during apoptosis triggered by Fas ligation. The issue was addressed by using aSMase-deficient and aSMase-corrected cell lines derived from Niemann-Pick disease (NPD) patients. Fas cross-linking elicited a rapid production of large amounts of complex a- and b-series species of gangliosides with a pattern and a chromatographic behavior as single bands reminiscent of brain gangliosides. The gangliosides were synthesized within the first ten minutes and completely disappeared within thirty minutes after stimulation. Noteworthy is the observation that GD3 was not the only ganglioside produced. The production of gangliosides and the onset of apoptotic hallmarks occurred similarly in both aSMase-deficient and aSMase-corrected NPD lymphoid cells, indicating that aSMase activation is not accountable for ganglioside generation. Hampering ganglioside production by inhibiting the key enzyme glucosylceramide synthase did not abrogate the apoptotic process. In addition, GM3 synthase-deficient lymphoid cells underwent Fas-induced apoptosis, suggesting that gangliosides are unlikely to play an indispensable role in transducing Fas-induced apoptosis of lymphoid cells. PMID:21629700

  8. Neuroprotective Ganglioside Derivatives

    DTIC Science & Technology

    2004-09-01

    In this study, neuroprotective ganglioside derivatives are studied in an attempt to devise neuroprotective agents targeted to specific points in cell...death pathways. GMl ganglioside and several of its chemically modified derivatives are neuroprotective in a variety of neurotoxic models. Here... ganglioside functional groups required for neuroprotection and blood-brain barrier (BBB) permeance are determined. Cell death mechanisms are also defined

  9. High-affinity anti-ganglioside IgG antibodies raised in complex ganglioside knockout mice: reexamination of GD1a immunolocalization.

    PubMed

    Lunn, M P; Johnson, L A; Fromholt, S E; Itonori, S; Huang, J; Vyas, A A; Hildreth, J E; Griffin, J W; Schnaar, R L; Sheikh, K A

    2000-07-01

    Gangliosides, sialic acid-bearing glycosphingolipids, are highly enriched in the vertebrate nervous system. Anti-ganglioside antibodies are associated with various human neuropathies, although the pathogenicity of these antibodies remains unproven. Testing the pathogenic role of anti-ganglioside antibodies will be facilitated by developing high-affinity IgG-class complement-fixing monoclonal anti-bodies against major brain gangliosides, a goal that has been difficult to achieve. In this study, mice lacking complex gangliosides were used as immune-naive hosts to raise anti-ganglioside antibodies. Wild-type mice and knockout mice with a disrupted gene for GM2/GD2 synthase (UDP-N-acetyl-D-galactosamine : GM3/GD3 N-acetyl-D-glactosaminyltransferase) were immunized with GD1a conjugated to keyhole limpet hemocyanin. The knockout mice produced a vigorous anti-GD1a IgG response, whereas wildtype littermates failed to do so. Fusion of spleen cells from an immunized knockout mouse with myeloma cells yielded numerous IgG anti-GD1a antibody-producing colonies. Ganglioside binding studies revealed two specificity classes; one colony representing each class was cloned and characterized. High-affinity monoclonal antibody was produced by each hybridoma : an IgG1 that bound nearly exclusively to GD1a and an IgG2b that bound GD1a, GT1b, and GT1aalpha. Both antibodies readily readily detected gangliosides via ELISA, TLC immune overlay, immunohistochemistry, and immunocytochemistry. In contrast to prior reports using anti-GD1a and anti-GT1b IgM class monoclonal antibodies, the new antibodies bound avidly to granule neurons in brain tissue sections and cell cultures. Mice lacking complex gangliosides are improved hosts for raising high-affinity, high-titer anti-ganglioside IgG antibodies for probing for the distribution and physiology of gangliosides and the pathophysiology of anti-ganglioside antibodies.

  10. Induction of GM1a/GD1b synthase triggers complex ganglioside expression and alters neuroblastoma cell behavior; a new tumor cell model of ganglioside function

    PubMed Central

    Dong, Lixian; Liu, Yihui; Colberg-Poley, Anamaris M.; Kaucic, Karen; Ladisch, Stephan

    2011-01-01

    Neuroblastoma is the most common extracranial solid tumor in children and tumor ganglioside composition has been linked to its biological and clinical behavior. We recently found that high expression of complex gangliosides that are products of the enzyme GM1a/GD1b synthase predicts a more favorable outcome in human neuroblastoma, and others have shown that complex gangliosides such as GD1a inhibit metastasis of murine tumors. To determine how a switch from structurally simple to structurally complex ganglioside expression affects neuroblastoma cell behavior, we engineered IMR32 human neuroblastoma cells, which contain almost exclusively (89%) the simple gangliosides (SG) GM2, GD2, GM3, and GD3, to overexpress the complex gangliosides (CG) GM1, GD1a, GD1b and GT1b, by stable retroviral-mediated transduction of the cDNA encoding GM1a/GD1b synthase. This strikingly altered cellular ganglioside composition without affecting total ganglioside content: There was a 23-fold increase in the ratio of complex to simple gangliosides in GM1a/GD1b synthase-transduced cells (IMR32-CG) vs. wild type (IMR32) or vector-transfected (IMR32-V) cells with essentially no expression of the clinical neuroblastoma marker, GD2, confirming effectiveness of this molecular switch from simple to complex ganglioside synthesis. Probing for consequences of the switch, we found that among functional properties of IMR32-CG cells, cell migration was inhibited and Rho/Rac1 activities were altered, while proliferation kinetics and cell differentiation were unaffected. These findings further implicate cellular ganglioside composition in determining cell migration characteristics of tumor cells. This IMR32 model system should be useful in delineating the impact of ganglioside composition on tumor cell function. PMID:21519903

  11. Induction of GM1a/GD1b synthase triggers complex ganglioside expression and alters neuroblastoma cell behavior; a new tumor cell model of ganglioside function.

    PubMed

    Dong, Lixian; Liu, Yihui; Colberg-Poley, Anamaris M; Kaucic, Karen; Ladisch, Stephan

    2011-05-01

    Neuroblastoma is the most common extracranial solid tumor in children and tumor ganglioside composition has been linked to its biological and clinical behavior. We recently found that high expression of complex gangliosides that are products of the enzyme GM1a/GD1b synthase predicts a more favorable outcome in human neuroblastoma, and others have shown that complex gangliosides such as GD1a inhibit metastasis of murine tumors. To determine how a switch from structurally simple to structurally complex ganglioside expression affects neuroblastoma cell behavior, we engineered IMR32 human neuroblastoma cells, which contain almost exclusively (89%) the simple gangliosides (SG) GM2, GD2, GM3, and GD3, to overexpress the complex gangliosides (CG) GM1, GD1a, GD1b and GT1b, by stable retroviral-mediated transduction of the cDNA encoding GM1a/GD1b synthase. This strikingly altered cellular ganglioside composition without affecting total ganglioside content: There was a 23-fold increase in the ratio of complex to simple gangliosides in GM1a/GD1b synthase-transduced cells (IMR32-CG) vs. wild type (IMR32) or vector-transfected (IMR32-V) cells with essentially no expression of the clinical neuroblastoma marker, GD2, confirming effectiveness of this molecular switch from simple to complex ganglioside synthesis. Probing for consequences of the switch, we found that among functional properties of IMR32-CG cells, cell migration was inhibited and Rho/Rac1 activities were altered, while proliferation kinetics and cell differentiation were unaffected. These findings further implicate cellular ganglioside composition in determining cell migration characteristics of tumor cells. This IMR32 model system should be useful in delineating the impact of ganglioside composition on tumor cell function.

  12. Disialoganglioside GD3-synthase over expression inhibits survival and angiogenesis of pancreatic cancer cells through cell cycle arrest at S-phase and disruption of integrin-β1-mediated anchorage.

    PubMed

    Mandal, Chandan; Sarkar, Sayantani; Chatterjee, Uttara; Schwartz-Albiez, Reinhard; Mandal, Chitra

    2014-08-01

    Gangliosides play important roles in the development, differentiation and proliferation of mammalian cells. They bind to other cell membrane components through their terminal sialic acids. Different gangliosides influence cellular functions based on the positions and linkages of sialic acids. Expression of gangliosides mainly depends on the status of sialic acid-modulatory enzymes, such as different types of sialyltransferases and sialidases. One such sialyltransferase, disialoganglioside GD3 synthase, is specifically responsible for the production of GD3. Pancreatic ductal adenocarcinoma, making up more than 90% of pancreatic cancers, is a fatal malignancy with poor prognosis. Despite higher sialylation status, the disialoganglioside GD3 level is very low in this cancer. However, the exact status and function of this disialoganglioside is still unknown. Here, we intended to study the intracellular mechanism of disialoganglioside GD3-induced apoptosis and its correlation with the adhesion and angiogenic pathways in pancreatic cancer. We demonstrated that disialoganglioside GD3 synthase-transfected cells showed enhanced apoptosis and it caused the arrest of these cells in the S-phase of the cell cycle. Integrins, a family of transmembrane proteins play important role in cell-cell recognition, invasion, adhesion and migration. disialoganglioside GD3 co-localised with integrin-β1 and thereby inhibited it's downstream signalling in transfected cells. Transfected cells exhibited inhibition of cell adhesion with extracellular matrix proteins. Enhanced GD3 expression down regulated angiogenesis-regulatory proteins and inhibited epidermal growth factor/vascular endothelial growth factor-driven angiogenic cell growth in these cells. Taken together, our study provides support for the GD3-induced cell cycle arrest, disruption of integrin-β1-mediated anchorage, inhibition of angiogenesis and thereby induced apoptosis in pancreatic cancer cells. Copyright © 2014 Elsevier Ltd

  13. Immunoglobulin G-class mouse monoclonal antibodies to major brain gangliosides.

    PubMed

    Schnaar, Ronald L; Fromholt, Susan E; Gong, Yanping; Vyas, Alka A; Laroy, Wouter; Wayman, Dawn M; Heffer-Lauc, Marija; Ito, Hiromi; Ishida, Hideharu; Kiso, Makoto; Griffin, John W; Shiekh, Kazim A

    2002-03-15

    Mice genetically engineered to lack complex gangliosides are improved hosts for raising antibodies against those gangliosides. We report the generation and characterization of nine immunoglobulin G (IgG)-class monoclonal antibodies (mAbs) raised against the four major brain gangliosides in mammals. These include (designated as ganglioside specificity-IgG subclass) two anti-GM1 mAbs (GM1-1, GM1-2b), three anti-GD1a mAbs (GD1a-1, GD1a-2a, GD1a-2b), one anti-GD1b mAb (GD1b-1), and three anti-GT1b mAbs (GT1b-1, GT1b-2a, GT1b-2b). Each mAb demonstrated high specificity, with little or no cross-reactivity with other major brain gangliosides. Enzyme-linked immunosorbent assay (ELISA) screening against 14 closely related synthetic and purified gangliosides confirmed the high specificity, with no significant cross-reactivity except that of the anti-GD1a mAbs for the closely related minor ganglioside GT1a alpha. All of the mAbs were useful for ELISA, TLC immunooverlay, and immunocytochemistry. Neural cells from wild-type rats and mice were immunostained to differing levels with the anti-ganglioside antibodies, whereas neural cells from mice engineered to lack complex gangliosides (lacking the ganglioside-specific biosynthetic enzyme UDP-GalNAc:GM3/GD3 N-acetylgalactosaminyltransferase) remained unstained, demonstrating that most of the mAbs react only with gangliosides and not with related structures on glycoproteins. These mAbs may provide useful tools for delineation of the expression and function of the major brain gangliosides and for probing the pathology of anti-ganglioside autoimmune diseases.

  14. Disialyl GD2 ganglioside suppresses ICAM-1-mediated invasiveness in human breast cancer MDA-MB231 cells

    PubMed Central

    Kwon, Kyung-Min; Chung, Tae-Wook; Kwak, Choong-Hwan; Choi, Hee-Jung; Kim, Kyung-Woon; Ha, Sun-Hyung; Cho, Seung-Hak; Lee, Young-Choon; Ha, Ki-Tae; Lee, Moon-Jo; Kim, Cheorl-Ho

    2017-01-01

    The disialoganglioside GD3 has been considered to be involved in tumor progression or suppression in various tumor cells. However, the significance of the biological functions of GD3 in breast cancer cells is still controversial. This prompted us to study the possible relationship(s) between GD3 expression and the metastatic potential of a breast cancer MDA-MB231 cells as an estrogen receptor negative (ER-) type. The human GD3 synthase cDNA was transfected into MDA-MB231 cells, and G-418 bulk selection was used to select cells stably overexpressing the GD3 synthase. In vitro invasion potentials of the GD3 synthase over-expressing cells (pc3-GD3s) were significantly suppressed when compared with control cells. Expression of intercellular adhesion molecule-1 (ICAM-1; CD54) was down-regulated in the pc3-GD3s cells and the decrease in ICAM-I expression is directly related to the decrease in invasiveness of the pc3-GD3s cells. Another type of ER negative SK-BR3 cells exhibited the similar level of ICAM-1 expression as MDA-MB231 cells, while the ER positive MCF-7 cells (ER+) showed the increased expression level of ICAM-1. Then, we investigated signaling pathways known to control ICAM-1 expression. No difference was observed in the phosphorylation of ERK and p38 between the pc3-GD3s and control cells (pc3), but the activation of AKT was inhibited in pc3-GD3s, and not in the control (pc3). In addition, the composition of total gangliosides was changed between control (pc3) and pc3-GD3s cells, as confirmed by HPTLC. The pc3-GD3s cells had an accumulation of the GD2 instead of the GD3. RT-PCR results showed that not only GD3 synthase, but also GM2/GD2 synthase (β4-GalNc T) expression was increased in pc3-GD3s cells. Overexpression of GD3 synthase suppresses the invasive potential of human breast cancer MDA-MB-231 cells through down-regulation of ICAM-1 and the crucial pathway to allow the apoptotic effect has been attributed to accumulation of the GD2 ganglioside. ER has

  15. Hydrolysis of milk gangliosides by infant-gut associated bifidobacteria determined by microfluidic chips and high-resolution mass spectrometry

    PubMed Central

    Lee, Hyeyoung; Garrido, Daniel; Mills, David A.; Barile, Daniela

    2014-01-01

    Gangliosides are receiving considerable attention because they participate in diverse biological processes. Milk gangliosides appear to block pathogen adhesion and modify the intestinal ecology of newborns. However, the interaction of milk gangliosides with gut bifidobacteria has been little investigated. The digestion products of a mixture of gangliosides isolated from milk following incubation with six strains of bifidobacteria were studied using nanoHPLC ChipQ-TOF MS. To understand ganglioside catabolism in vitro, the two major milk gangliosides—GM3 and GD3—remaining in the media after incubation with bifidobacteria were quantified. Individual gangliosides were identified through post-processing precursor ion scans, and quantitated with the “find by molecular feature” algorithm of MassHunter Qualitative Analysis software. B. infantis and B. bifidum substantially degraded the GM3 and GD3, whereas B. longum subsp. longum and B. animalis subsp. lactis only showed moderate degradation. MALDI FTICR MS analysis enabled a deeper investigation of the degradation and identified ganglioside degradation specifically at the outer portions of the glycan molecules. These results indicate that certain infant gut-associated bifidobacteria have the ability to degrade milk gangliosides releasing sialic acid, and that these glycolipids could play a prebiotic role in the infant gut. PMID:24519724

  16. A new sialic acid analogue, 9-O-acetyl-deaminated neuraminic acid, and alpha -2,8-linked O-acetylated poly(N-glycolylneuraminyl) chains in a novel polysialoglycoprotein from salmon eggs.

    PubMed

    Iwasaki, M; Inoue, S; Troy, F A

    1990-02-15

    A new polysialoglycoprotein, designated PSGP(On), was isolated from the unfertilized eggs of the kokanee salmon, Oncorhynchus nerka adonis. 400-MHz 1H NMR analyses showed the O. nerka adonis PSGP contained alpha -2,8-linked oligo- and polysialic acid (polySia) chains that were made up of 4-O-Ac-, 7-O-Ac-, and 9-O-Ac esters of N-glycolylneuraminic acid (Neu5Gc) residues. The presence of a new sialic acid derivative, identified by 1H NMR as 9-O-acetyl-2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (trivial name, 9-O-acetyldeaminated neuraminic acid; 9-O-Ac-KDN), was also shown to be present as a minor component. The O-acetylated KDN residues appear to cap the nonreducing termini of the O-acetylated poly(Neu5Gc) chains. The O-acetylated polySia chains were resistant to depolymerization by bacterial exosialidases and a bacteriophage-derived endo-N-acylneuraminidase that is specific for catalyzing the hydrolysis of alpha -2,8-linkages in polySia containing either N-acetylneuraminic acid or Neu5Gc residues. After de-O-acetylation by mild alkali, the polySia chains were sensitive to digestion by endo-N-acylneuraminidase, yet partially resistant to exosialidase. These data confirm the alpha -2,8-ketosidic linkage in these chains and the nonreducing terminal location of the KDN residues. These results extend further the range of structural diversity in polySia-containing glycoconjugates, and in the family of naturally occurring sialic acids. They also suggest that the O-acetylated Neu5Gc and 9-O-Ac-KDN residues may have an important role during oogenesis.

  17. Increased catabolism and decreased unsaturation of ganglioside in patients with inflammatory bowel disease

    PubMed Central

    Miklavcic, John J; Hart, Tasha DL; Lees, Gordon M; Shoemaker, Glen K; Schnabl, Kareena L; Larsen, Bodil MK; Bathe, Oliver F; Thomson, Alan BR; Mazurak, Vera C; Clandinin, M Tom

    2015-01-01

    AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn’s disease (n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps (n = 6) and colorectal cancer (n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine (PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A (HEXA) and sialidase-3 (NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. RESULTS: Relative GM3 ganglioside content was 2-fold higher (P < 0.05) in intestine from patients with inflammatory bowel disease (IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue (P < 0.05). Control intestine exhibited 3-fold higher (P < 0.01) relative GD1a ganglioside content than IBD intestine. GD3 and GD1a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine (P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold (P < 0.05) and NEU3 was

  18. Increased catabolism and decreased unsaturation of ganglioside in patients with inflammatory bowel disease.

    PubMed

    Miklavcic, John J; Hart, Tasha D L; Lees, Gordon M; Shoemaker, Glen K; Schnabl, Kareena L; Larsen, Bodil M K; Bathe, Oliver F; Thomson, Alan B R; Mazurak, Vera C; Clandinin, M Tom

    2015-09-21

    To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease (n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps (n = 6) and colorectal cancer (n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine (PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A (HEXA) and sialidase-3 (NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. Relative GM3 ganglioside content was 2-fold higher (P < 0.05) in intestine from patients with inflammatory bowel disease (IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue (P < 0.05). Control intestine exhibited 3-fold higher (P < 0.01) relative GD1a ganglioside content than IBD intestine. GD3 and GD1a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine (P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold (P < 0.05) and NEU3 was increased 8.3-fold (P < 0

  19. Monoclonal antibodies raised against Guillain-Barré syndrome–associated Campylobacter jejuni lipopolysaccharides react with neuronal gangliosides and paralyze muscle-nerve preparations

    PubMed Central

    Goodyear, Carl S.; O’Hanlon, Graham M.; Plomp, Jaap J.; Wagner, Eric R.; Morrison, Ian; Veitch, Jean; Cochrane, Lynne; Bullens, Roland W. M.; Molenaar, Peter C.; Conner, Joe; Willison, Hugh J.

    1999-01-01

    Guillain-Barré syndrome and its variant, Miller-Fisher syndrome, are acute, postinfectious, autoimmune neuropathies that frequently follow Campylobacter jejuni enteritis. The pathogenesis is believed to involve molecular mimicry between sialylated epitopes on C. jejuni LPSs and neural gangliosides. More than 90% of Miller-Fisher syndrome cases have serum anti-GQ1b and anti-GT1a ganglioside antibodies that may also react with other disialylated gangliosides including GD3 and GD1b. Structural studies on LPS from neuropathy-associated C. jejuni strains have revealed GT1a-like and GD3-like core oligosaccharides. To determine whether this structural mimicry results in pathogenic autoantibodies, we immunized mice with GT1a/GD3-like C. jejuni LPS and then cloned mAb’s that reacted with both the immunizing LPS and GQ1b/GT1a/GD3 gangliosides. Immunohistology demonstrated antibody binding to ganglioside-rich sites including motor nerve terminals. In ex vivo electrophysiological studies of nerve terminal function, application of antibodies either ex vivo or in vivo via passive immunization induced massive quantal release of acetylcholine, followed by neurotransmission block. This effect was complement-dependent and associated with extensive deposits of IgM and C3c at nerve terminals. These data provide strong support for the molecular mimicry hypothesis as a mechanism for the induction of cross-reactive pathogenic anti-ganglioside/LPS antibodies in postinfectious neuropathies. PMID:10491405

  20. Neuroprotective Ganglioside Derivatives

    DTIC Science & Technology

    2003-09-01

    In this study, neuroprotective ganglioside derivatives are examined so they can be targeted to specific points in cell death pathways. Here... ganglioside functional groups required for neuroprotection and blood-brain barrier permeance are determined. Cell death mechanisms and the mechanism(s) by...which semisynthetic gangliosides intervene in the cell death process are also studied. In the second year C2, C4, CS, C14, C20, and C26 fatty acid GMl

  1. Gangliosides stimulate bradykinin B2 receptors to promote calmodulin kinase II-mediated neuronal differentiation.

    PubMed

    Kanatsu, Yoshinori; Chen, Nai Hong; Mitoma, Junya; Nakagawa, Tetsuto; Hirabayashi, Yoshio; Higashi, Hideyoshi

    2012-07-01

    Gangliosides mediate neuronal differentiation and maturation and are indispensable for the maintenance of brain function and survival. As part of our ongoing efforts to understand signaling pathways related to ganglioside function, we recently demonstrated that neuronal cells react to exogenous gangliosides GT1b and GD1b. Both of these gangliosides are enriched in the synapse-forming area of the brain and induce Ca(2+) release from intracellular stores, activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and activation of cdc42 to promote reorganization of cytoskeletal actin and dendritic differentiation. Here, we show that bradykinin B2 receptors transduce these reactions as a mediator for ganglioside glycan signals. The B2 antagonist Hoe140 inhibited ganglioside-induced CaMKII activation, actin reorganization and early development of axon- and dendrite-like processes of primary cultured hippocampal neurons. Furthermore, we confirmed by yeast reporter assay that major b-series gangliosides, GT1b, GD1b and GD3, stimulated B2 bradykinin receptors. We hypothesize that this B2 receptor-mediated ganglioside signal transduction pathway is one mechanism that modulates neuronal differentiation and maturation.

  2. Effect of Gd3+ on the colloidal stability of liposomes.

    PubMed

    Sabín, Juan; Prieto, Gerardo; Sennato, Simona; Ruso, Juan M; Angelini, Roberta; Bordi, Federico; Sarmiento, Félix

    2006-09-01

    Lanthanide ions such as La3+ and Gd3+ are well known to have large effects on the structure of phospholipid membranes. Unilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC) were prepared by sonication method and confirmed by transmission electron microscopy. The effects of concentration of gadolinium ions Gd3+ on DPPC unilamellar vesicles in aqueous media were studied by different techniques. As physical techniques, photon correlation spectroscopy, electrophoretic mobility, and differential scanning calorimetry were used. The theoretical predictions of the colloidal stability of liposomes were followed using the Derjaguin-Landau-Verwey-Overbeek theory. Changes in the size of liposomes and high polydispersities values were observed as Gd3+ concentration increases, suggesting that this cation induces the aggregation of vesicles. Electrophoretic mobility measurements on unilamellar vesicles as a function of Gd3+ ion concentration show that the vesicles adsorb Gd3+ ions. Above Gd3+ concentrations of 0.1 mol dm-3, the zeta potential and light scattering measurements indicate the beginning of aggregation process. For comparison with similar phospholipids, the zeta potential of phosphatidylcholine interacting with Gd3+ was measured, showing an analogous behavior. Differential scanning calorimetry has been used to determine the effect of Gd3+ on the transition temperature (Tc) and on the enthalpy (DeltaHc) associated with the process.

  3. Purification of human milk gangliosides by silica gel chromatography and analysis of trifluoroacetate derivatives by gas chromatography.

    PubMed

    Laegreid, A; Kolstø Otnaess, A B; Bryn, K

    1986-04-25

    Two of the main gangliosides in human milk were purified by silica gel (230-400 mesh) column chromatography. The gangliosides were identified as GD3 and GM3 by methanolysis (2 M hydrochloric acid; 60 or 85 degrees C) and gas chromatography of trifluoroacetate derivatives on a fused-silica capillary column. The molar ratios of galactose, glucose and sialic acid were 1:1:2 and 1:1:1, respectively, and the sequence in both gangliosides comprised sialic acid--galactose--glucose--ceramide, as indicated by the time course of cleavage of individual components during methanolysis at 60 degrees C.

  4. Gangliosides and hearing.

    PubMed

    Inokuchi, Jin-Ichi; Go, Shinji; Yoshikawa, Misato; Strauss, Kevin

    2017-10-01

    Severe auditory impairment observed in GM3 synthase-deficient mice and humans indicates that glycosphingolipids, especially sialic-acid containing gangliosides, are indispensable for hearing. Gangliosides associate with glycoproteins to form membrane microdomains, the composition of which plays a special role in maintaining the structural and functional integrity of hair cells. These microdomains, also called lipid rafts, connect with intracellular signaling and cytoskeletal systems to link cellular responses to environmental cues. During development, ganglioside species are expressed in distinctive spatial and temporal patterns throughout the cochlea. In both mice and humans, blocking particular steps of ganglioside metabolism produces distinctive neurological and auditory phenotypes. Thus each ganglioside species may have specific, non-overlapping functions within the cochlea, central auditory network, and brain. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Escherichia coli O157:H7 Strain EDL933 Harbors Multiple Functional Prophage-Associated Genes Necessary for the Utilization of 5-N-Acetyl-9-O-Acetyl Neuraminic Acid as a Growth Substrate

    PubMed Central

    Saile, Nadja; Voigt, Anja; Kessler, Sarah; Stressler, Timo; Fischer, Lutz

    2016-01-01

    ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) O157:H7 strain EDL933 harbors multiple prophage-associated open reading frames (ORFs) in its genome which are highly homologous to the chromosomal nanS gene. The latter is part of the nanCMS operon, which is present in most E. coli strains and encodes an esterase which is responsible for the monodeacetylation of 5-N-acetyl-9-O-acetyl neuraminic acid (Neu5,9Ac2). Whereas one prophage-borne ORF (z1466) has been characterized in previous studies, the functions of the other nanS-homologous ORFs are unknown. In the current study, the nanS-homologous ORFs of EDL933 were initially studied in silico. Due to their homology to the chromosomal nanS gene and their location in prophage genomes, we designated them nanS-p and numbered the different nanS-p alleles consecutively from 1 to 10. The two alleles nanS-p2 and nanS-p4 were selected for production of recombinant proteins, their enzymatic activities were investigated, and differences in their temperature optima were found. Furthermore, a function of these enzymes in substrate utilization could be demonstrated using an E. coli C600ΔnanS mutant in a growth medium with Neu5,9Ac2 as the carbon source and supplementation with the different recombinant NanS-p proteins. Moreover, generation of sequential deletions of all nanS-p alleles in strain EDL933 and subsequent growth experiments demonstrated a gene dose effect on the utilization of Neu5,9Ac2. Since Neu5,9Ac2 is an important component of human and animal gut mucus and since the nutrient availability in the large intestine is limited, we hypothesize that the presence of multiple Neu5,9Ac2 esterases provides them a nutrient supply under certain conditions in the large intestine, even if particular prophages are lost. IMPORTANCE In this study, a group of homologous prophage-borne nanS-p alleles and two of the corresponding enzymes of enterohemorrhagic E. coli (EHEC) O157:H7 strain EDL933 that may be important to provide

  6. Synthesis of ganglioside epitopes for oligosaccharide specific immunoadsorption therapy of Guillian-Barré syndrome.

    PubMed

    Andersen, Søren M; Ling, Chang-Chun; Zhang, Ping; Townson, Kate; Willison, Hugh J; Bundle, David R

    2004-04-21

    Guillain-Barré syndrome is a postinfectious, autoimmune neuropathy resulting in neuromuscular paralysis. Auto-antibodies, often induced by bacterial infection, bind to human gangliosides possessing monosialoside and diasialoside epitopes and impair the function of nerve junctions, where these ganglioside structures are highly enriched. Truncated gangliosides representive of GD3, GQ1b and GM2 epitopes have been synthesized as methyl glycosides and as a glycosides of an eleven carbon tether. The synthetic oligosaccharide ligands are structural mimics of these highly complex ganglioside epitopes and via their ability to neutralize or remove auto-antibodies have the potential for therapy, either as soluble blocking ligands administered systemically, or as immuno-affinity ligands for use as extracorporeal immunoadsorbents.

  7. b-Series gangliosides crucially regulate leptin secretion in adipose tissues.

    PubMed

    Ji, Shuting; Ohkawa, Yuki; Tokizane, Kyohei; Ohmi, Yuhsuke; Banno, Ryoichi; Furukawa, Keiko; Kiyama, Hiroshi; Furukawa, Koichi

    2015-04-03

    Gangliosides are widely involved in the regulation of cells and organs. However, little is known about their roles in leptin secretion from adipose tissues. Genetic deletion of b-series gangliosides resulted in the marked reduction of serum leptin. Expression analysis of leptin revealed that leptin accumulated in the adipose tissues of GD3 synthase-knockout (GD3S KO) mice. Analysis of primary cultured stromal vascular fractions (SVF) derived from GD3S KO mice revealed that leptin secretion was reduced, although leptin amounts in cells were increased compared with those of wild type. Interestingly, addition of b-series gangliosides to the culture medium of differentiated SVF resulted in the restoration of leptin secretion. Results of methyl-β-cyclodextrin treatment of differentiated 3T3-L1 cells as well as immunocytostaining of leptin and caveolin-1 suggested that b-series gangliosides regulate the leptin secretion from adipose tissues in lipid rafts. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Roles for UDP-GlcNAc 2-epimerase/ManNAc 6-kinase outside of sialic acid biosynthesis: modulation of sialyltransferase and BiP expression, GM3 and GD3 biosynthesis, proliferation, and apoptosis, and ERK1/2 phosphorylation.

    PubMed

    Wang, Zhiyun; Sun, Zhonghui; Li, Adrienne V; Yarema, Kevin J

    2006-09-15

    Roles for UDP-GlcNAc 2-epimerase/ManNAc 6-kinase (GNE) beyond controlling flux into the sialic acid biosynthetic pathway by converting UDP-GlcNAc to N-acetylmannosamine are described in this report. Overexpression of recombinant GNE in human embryonic kidney (HEK AD293) cells led to an increase in mRNA levels for ST3Gal5 (GM3 synthase) and ST8Sia1 (GD3 synthase) as well as the biosynthetic products of these sialyltransferases, the GM3 and GD3 gangliosides. Conversely, down-regulation of GNE by RNA interference methods had the opposite, but consistent, effect of lowering ST3Gal5 and ST8Sia1 mRNAs and reducing GM3 and GD3 levels. Control experiments ensured that GNE-mediated changes in sialyltransferase expression and ganglioside biosynthesis were not the result of altered flux through the sialic acid pathway. Interestingly, exogenous GM3 and GD3 also changed the expression of GNE and led to reduced ST3Gal5 and ST8Sia1 mRNA levels, demonstrating a reciprocating feedback mechanism where gangliosides regulate upstream biosynthetic enzymes. Cellular responses to the GNE-mediated changes in ST3Gal5 and ST8Sia1 expression and GM3 and GD3 levels were investigated next. Conditions that led to reduced ganglioside production (e.g. short hairpin RNA exposure) stimulated proliferation, whereas conditions that resulted in increased ganglioside levels (e.g. recombinant GNE and exogenous gangliosides) led to reduced proliferation with a concomitant increase in apoptosis. Finally, changes to BiP expression and ERK1/2 phosphorylation consistent with apoptosis and proliferation, respectively, were observed. These results provide examples of specific biochemical pathways, other than sialic acid metabolism, that are influenced by GNE.

  9. Large scale biosynthesis of ganglioside analogues by RERF-LC-AI cells cultured in HYPERFlask.

    PubMed

    Shimura, Yumiko; Suzuki, Junya; Muraoka, Miho; Kasuya, Maria Carmelita Zulueta; Matsuoka, Koji; Hatanaka, Kenichi

    2012-01-01

    The efficient production of ganglioside analogues was accomplished using RERF-LC-AI cells cultured in HYPERFlask (High Yield PERformance Flask). Eight kinds of ganglioside analogues (GM3, GM2, sialylparagloboside, GD3, di-sialylated lacto-N-tetraose, and another three kinds of analogues with intricate structures) were synthesized by the saccharide primer method using lung squamous-cell carcinoma line RERF-LC-AI and 12-azidododecyl β-lactoside primer. The yield for each analogue obtained using HYPERFlask was higher than yields obtained from 100-mm dishes.

  10. Lactational changes in concentration and distribution of ganglioside molecular species in human breast milk from Chinese mothers.

    PubMed

    Ma, Lin; Liu, Xihong; MacGibbon, Alastair K H; Rowan, Angela; McJarrow, Paul; Fong, Bertram Y

    2015-11-01

    Gangliosides play a critical role in human brain development and function. Human breast milk (HBM) is an important dietary source of gangliosides for the growing infant. In this study, ganglioside concentrations were measured in the breast milk from a cross-sectional sample of Chinese mothers over an 8-month lactation period. The average total ganglioside concentration increased from 13.1 mg/l during the first month to 20.9 mg/l by 8 months of lactation. The average concentration during the typically solely breast-feeding period of 1‒6 months was 18.9 mg/l. This is the first study to report the relative distribution of the individual ganglioside molecular species through lactation for any population group. The ganglioside molecular species are made up of different fatty acid moieties that influence the physical properties of these gangliosides, and hence affect their function. The GM(3) molecular species containing long-chain acyl fatty acids had the most prominent changes, increasing in both concentration and relative distribution. The equivalent long-chain acyl fatty acid GD(3) molecular species typically decreased in concentration and relative distribution. The lactational trends for both concentration and relative distribution for the very long-chain acyl fatty acid molecular species were more varied. The major GM(3) and GD(3) molecular species during lactation were d40:1 and d42:1, respectively. An understanding of ganglioside molecular species distribution in HBM is essential for accurate application of mass spectrometry methods for ganglioside quantification.

  11. Enhanced expression of membrane-associated sialidase Neu3 decreases GD3 and increases GM3 on the surface of Jurkat cells during etoposide-induced apoptosis.

    PubMed

    Azuma, Yutaro; Sato, Hirotaka; Higai, Koji; Matsumoto, Kojiro

    2007-09-01

    We previously reported that, in Jurkat human T cells, the topoisomerase II inhibitor etoposide enhances sialidase activity and reduces cell surface sialic acid levels at an early stage of apoptosis and that the decreases in sialic acid are suppressed by the sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid [Azuma Y., et al., Glycoconj. J., 17, 301-306 (2000)]. In the current studies, we treated Jurkat cells with etoposide and examined the changes in the cell surface levels of gangliosides GM1, GM2, GM3, GD1a, and GD3 at physiological pH using anti-ganglioside antibodies. We also examined the sialidase activity on the cell surface using 4-methylumbelliferyl N-acetylneuraminic acid and measured the mRNA expression of the plasma membrane-associated sialidase Neu3 and the lysozomal Neu1 using real-time PCR. We found an increase in GM3 and a decrease in GD3 during the early stage (4 h) of etoposide-induced apoptosis that preceded the increase in cell surface exposure of phosphatidylserine (4 to 6 h). The caspase 3 inhibitor acetyl-Asp-Glu-Val-Asp-aldehyde significantly suppressed changes in GM3 and GD3 and blocked the enhanced cell surface sialidase activity. Furthermore, etoposide caused a gradual up-regulation of Neu3 mRNA expression but not Neu1 mRNA expression. Enhanced Neu3 mRNA expression was suppressed in the presence of caspase 3 inhibitor. These results indicate that Neu3 is up-regulated in Jurkat cells undergoing etoposide-induced apoptosis through intracellular signaling events downstream of caspase 3 activation and that enhanced Neu3 activity is closely related to the changes of cell surface ganglioside composition.

  12. Ganglioside Profiling of the Human Retina: Comparison with Other Ocular Structures, Brain and Plasma Reveals Tissue Specificities

    PubMed Central

    Sibille, Estelle; Berdeaux, Olivier; Martine, Lucy; Bron, Alain M.; Creuzot-Garcher, Catherine P.; He, Zhiguo; Thuret, Gilles; Bretillon, Lionel; Masson, Elodie A. Y.

    2016-01-01

    Gangliosides make a wide family of glycosphingolipids, highly heterogeneous in both the ceramide moiety and the oligosaccharide chain. While ubiquitously expressed in mammalian tissues, they are particularly abundant in the brain and the peripheral nervous system. Gangliosides are known to play a crucial role in the development, maintenance and functional integrity of the nervous system. However, the expression and roles of gangliosides in the retina, although often considered as a window on the brain, has been far less studied. We performed an in-depth analysis of gangliosides of the human retina, especially using powerful LC/MS methods. We compared the pattern of ganglioside classes and ceramide molecular species of this tissue with other ocular structures and with brain and plasma in elderly human individuals. About a hundred of ganglioside molecular species among 15 distinct classes were detected illustrating the huge structural diversity of these compounds. The retina exhibited a very diverse ganglioside profile and shared several common features with the brain (prominence of tetraosylgangliosides, abundance of d20:1 long chain base and 18:0 fatty acid…). However, the retina stood out with the specific expression of GD3, GT3 and AcGT3, which further presented a peculiar molecular species distribution. The unique ganglioside pattern we observed in the human retina suggests that these ganglioside species play a specific role in the structure and function of this tissue. This lipidomic study, by highlighting retina specific ganglioside species, opens up novel research directions for a better understanding of the biological role of gangliosides in the retina. PMID:27997589

  13. Ganglioside Profiling of the Human Retina: Comparison with Other Ocular Structures, Brain and Plasma Reveals Tissue Specificities.

    PubMed

    Sibille, Estelle; Berdeaux, Olivier; Martine, Lucy; Bron, Alain M; Creuzot-Garcher, Catherine P; He, Zhiguo; Thuret, Gilles; Bretillon, Lionel; Masson, Elodie A Y

    2016-01-01

    Gangliosides make a wide family of glycosphingolipids, highly heterogeneous in both the ceramide moiety and the oligosaccharide chain. While ubiquitously expressed in mammalian tissues, they are particularly abundant in the brain and the peripheral nervous system. Gangliosides are known to play a crucial role in the development, maintenance and functional integrity of the nervous system. However, the expression and roles of gangliosides in the retina, although often considered as a window on the brain, has been far less studied. We performed an in-depth analysis of gangliosides of the human retina, especially using powerful LC/MS methods. We compared the pattern of ganglioside classes and ceramide molecular species of this tissue with other ocular structures and with brain and plasma in elderly human individuals. About a hundred of ganglioside molecular species among 15 distinct classes were detected illustrating the huge structural diversity of these compounds. The retina exhibited a very diverse ganglioside profile and shared several common features with the brain (prominence of tetraosylgangliosides, abundance of d20:1 long chain base and 18:0 fatty acid…). However, the retina stood out with the specific expression of GD3, GT3 and AcGT3, which further presented a peculiar molecular species distribution. The unique ganglioside pattern we observed in the human retina suggests that these ganglioside species play a specific role in the structure and function of this tissue. This lipidomic study, by highlighting retina specific ganglioside species, opens up novel research directions for a better understanding of the biological role of gangliosides in the retina.

  14. Gangliosides are essential in the protection of inflammation and neurodegeneration via maintenance of lipid rafts: elucidation by a series of ganglioside-deficient mutant mice.

    PubMed

    Ohmi, Yuhsuke; Tajima, Orie; Ohkawa, Yuki; Yamauchi, Yoshio; Sugiura, Yasuo; Furukawa, Keiko; Furukawa, Koichi

    2011-03-01

    Gangliosides are considered to be involved in the maintenance and repair of nervous tissues. Recently, novel roles of gangliosides in the regulation of complement system were reported by us. In this study, we compared complement activation, inflammatory reaction and disruption of glycolipid-enriched microdomain (GEM)/rafts among various mutant mice of ganglioside synthases, i.e. GM2/GD2 synthase knockout (KO), GD3 synthase KO, double KO (DKO) of these two enzymes and wild type. Up-regulation of complement-related genes, deposits of C1q, proliferation of astrocytes and infiltration of microglia also showed similar gradual severity depending on the defects in ganglioside compositions. In the expression of inflammatory cytokines such as IL-1β and tumor necrosis factor α, only DKO showed definite up-regulation. Immunoblotting of fractions from sucrose density gradient ultracentrifugation revealed that lipid raft markers such as caveolin-1 and flotillin-1 tended to disperse from the raft fractions with intensities of DKO > GM2/GD2 synthase KO > GD3 synthase KO > wild type. Decay-accelerating factor and neural cell adhesion molecule tended to disappear from the raft fraction. Phospholipids and cholesterol also tended to decrease in GEM/rafts in GM2/GD2 synthase KO and DKO, although total amounts were almost equivalent. These results indicate that destruction of GEM/rafts is caused by ganglioside deficiency with gradual intensity depending on the degree of defects of their compositions. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  15. Studies on Human Platelet Gangliosides

    PubMed Central

    Marcus, Aaron J.; Ullman, Harris L.; Safier, Lenore B.

    1972-01-01

    Gangliosides, glycosphingolipids which contain sialic acid, were studied in human platelets. They represented 0.5% of the platelet lipids and accounted for 6% of the total neuraminic acid content of platelets. Three major ganglioside fractions were identified and characterized. Ganglioside I was hematoside (G6) and comprised 92% of the platelet gangliosides. It contained glucose, galactose, and sialic acid in molar ratios of 1:1:1 and no hexosamine. The major fatty acid was behenate (22:0). Ganglioside I was also identified in isolated platelet granules and membranes. Ganglioside II (5%) contained glucose, galactose, sialic acid, and hexosamines (molar ratios 1:2:1:1). The hexosamines were glucosamine (72%) and galactosamine (28%). It was therefore designated as ganglioside lacto-N-neotetraose. Ganglioside III (2%) contained disialosyllactosyl ceramide (G3A) as well as two other gangliosides which could not be precisely characterized. Gangliosides I, II, and III were susceptible to the action of Clostridium perfringens neuraminidase as evidenced by full recovery of sialic acid in its free form after incubation. Neutral platelet glycolipids were qualitatively examined by thin-layer chromatography. The major component was lactosyl ceramide. Interactions of gangliosides I and III and serotonin-14C were examined in an equilibrium dialysis system at 4°C. The gangliosides bound serotonin-14C in relatively small quantities, whereas control lipids were negative. The binding was essentially unchanged by reverse dialysis, ultracentrifugation and subsequent thin-layer chromatography. The results are comparable to the previously observed nonmetabolic interactions between whole platelets and serotonin in the cold. It is suggested that the orientation and specific distribution of platelet membrane glycolipids may be important determinants of the unique surface properties of platelets. Images PMID:4341436

  16. Neutral glycolipid and ganglioside composition of type-1 and type-2 astrocytes from rat cerebral hemisphere.

    PubMed

    Murakami, K; Asou, H; Adachi, T; Takagi, T; Kunimoto, M; Saito, H; Uyemura, K

    1999-02-01

    We reported previously that the major gangliosides in primary mixed-type astrocyte cultures are GM3 and GD3. To obtain more information regarding the exact distribution of glycosphingolipids in different types of astrocytes, we established a line of type-1 astrocytes that are characterized by a Ran-2 positive, broad flat morphology, and by the absence of binding to A2B5 antibodies. We also purified O-2A progenitor cells by immunopanning and cultured them in the presence of 10% newborn calf serum. They differentiated into type-2 astrocytes that were identified by immunostaining for each of GD3, A2B5, and GFAP. Using these cell cultures, we demonstrate that the major gangliosides were GM3 in type-1 astrocytes and GM3 and GD3 in type-2 astrocytes. In addition, a set of neutral glycolipids was identified based on the HP-TLC migration properties of CMH, CDH, CTH, and Glob, but the component distribution of these glycolipids is related to that of glycolipids of astrocytes. A marked increase in the expression of CTH and Glob was shown in type-2 astrocytes. The amount of neutral glycolipid-sugar was higher in the type-2 astrocytes than in the type-1 astrocytes. These results suggest that the increase in the total glycosphingolipid content and the change in the neutral glycolipid composition produced by type-2 astrocytes may be related to their biological functions and the cellular compositions.

  17. The Effects of Age and Ganglioside Composition on the Rate of Motor Nerve Terminal Regeneration Following Antibody-Mediated Injury in Mice

    PubMed Central

    Rupp, Angie; Cunningham, Madeleine E; Yao, Denggao; Furukawa, Koichi; Willison, Hugh J

    2013-01-01

    Gangliosides are glycosphingolipids highly enriched in neural plasma membranes, where they mediate a diverse range of functions and can act as targets for auto-antibodies present in human immune-mediated neuropathy sera. The ensuing autoimmune injury results in axonal and motor nerve terminal (mNT) degeneration. Both aging and ganglioside-deficiency have been linked to impaired axonal regeneration. To assess the effects of age and ganglioside expression on mNT regeneration in an autoimmune injury paradigm, anti-ganglioside antibodies and complement were applied to young adult and aged mice wildtype (WT) mice, mice deficient in either b- and c-series (GD3sKO) or mice deficient in all complex gangliosides (GM2sKO). The extent of mNT injury and regeneration was assessed immediately or after 5 days, respectively. Depending on ganglioside expression and antibody-specificity, either a selective mNT injury or a combined injury of mNTs and neuromuscular glial cells was elicited. Immediately after induction of the injury, between 1.5% and 11.8% of neuromuscular junctions (NMJs) in the young adult groups exhibited healthy mNTs. Five days later, most NMJs, regardless of age and strain, had recovered their mNTs. No significant differences could be observed between young and aged WT and GM2sKO mice; aged GD3sKO showed a mildly impaired rate of mNT regeneration when compared with their younger counterparts. Comparable rates were observed between all strains in the young and the aged mice. In summary, the rate of mNT regeneration following anti-ganglioside antibody and complement-mediated injury does not differ majorly between young adult and aged mice irrespective of the expression of particular gangliosides. Synapse 67:382–389, 2013. © 2013 Wiley Periodicals, Inc. PMID:23401234

  18. The effects of age and ganglioside composition on the rate of motor nerve terminal regeneration following antibody-mediated injury in mice.

    PubMed

    Rupp, Angie; Cunningham, Madeleine E; Yao, Denggao; Furukawa, Koichi; Willison, Hugh J

    2013-07-01

    Gangliosides are glycosphingolipids highly enriched in neural plasma membranes, where they mediate a diverse range of functions and can act as targets for auto-antibodies present in human immune-mediated neuropathy sera. The ensuing autoimmune injury results in axonal and motor nerve terminal (mNT) degeneration. Both aging and ganglioside-deficiency have been linked to impaired axonal regeneration. To assess the effects of age and ganglioside expression on mNT regeneration in an autoimmune injury paradigm, anti-ganglioside antibodies and complement were applied to young adult and aged mice wildtype (WT) mice, mice deficient in either b- and c-series (GD3sKO) or mice deficient in all complex gangliosides (GM2sKO). The extent of mNT injury and regeneration was assessed immediately or after 5 days, respectively. Depending on ganglioside expression and antibody-specificity, either a selective mNT injury or a combined injury of mNTs and neuromuscular glial cells was elicited. Immediately after induction of the injury, between 1.5% and 11.8% of neuromuscular junctions (NMJs) in the young adult groups exhibited healthy mNTs. Five days later, most NMJs, regardless of age and strain, had recovered their mNTs. No significant differences could be observed between young and aged WT and GM2sKO mice; aged GD3sKO showed a mildly impaired rate of mNT regeneration when compared with their younger counterparts. Comparable rates were observed between all strains in the young and the aged mice. In summary, the rate of mNT regeneration following anti-ganglioside antibody and complement-mediated injury does not differ majorly between young adult and aged mice irrespective of the expression of particular gangliosides. Copyright © 2013 Wiley Periodicals, Inc.

  19. Molecular subtyping of metastatic melanoma based on cell ganglioside metabolism profiles.

    PubMed

    Tringali, Cristina; Silvestri, Ilaria; Testa, Francesca; Baldassari, Paola; Anastasia, Luigi; Mortarini, Roberta; Anichini, Andrea; López-Requena, Alejandro; Tettamanti, Guido; Venerando, Bruno

    2014-08-01

    In addition to alterations concerning the expression of oncogenes and onco-suppressors, melanoma is characterized by the presence of distinctive gangliosides (sialic acid carrying glycosphingolipids). Gangliosides strongly control cell surface dynamics and signaling; therefore, it could be assumed that these alterations are linked to modifications of cell behavior acquired by the tumor. On these bases, this work investigated the correlations between melanoma cell ganglioside metabolism profiles and the biological features of the tumor and the survival of patients. Melanoma cell lines were established from surgical specimens of AJCC stage III and IV melanoma patients. Sphingolipid analysis was carried out on melanoma cell lines and melanocytes through cell metabolic labeling employing [3-3H]sphingosine and by FACS. N-glycolyl GM3 was identified employing the 14 F7 antibody. Gene expression was assayed by Real Time PCR. Cell invasiveness was assayed through a Matrigel invasion assay; cell proliferation was determined through the soft agar assay, MTT, and [3H] thymidine incorporation. Statistical analysis was performed using XLSTAT software for melanoma hierarchical clustering based on ganglioside profile, the Kaplan-Meier method, the log-rank (Mantel-Cox) test, and the Mantel-Haenszel test for survival analysis. Based on the ganglioside profiles, through a hierarchical clustering, we classified melanoma cells isolated from patients into three clusters: 1) cluster 1, characterized by high content of GM3, mainly in the form of N-glycolyl GM3, and GD3; 2) cluster 2, characterized by the appearance of complex gangliosides and by a low content of GM3; 3) cluster 3, which showed an intermediate phenotype between cluster 1 and cluster 3. Moreover, our data demonstrated that: a) a correlation could be traced between patients' survival and clusters based on ganglioside profiles, with cluster 1 showing the worst survival; b) the expression of several enzymes (sialidase NEU3

  20. Alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 can support immune responses toward tumors overexpressing ganglioside D3 in mice.

    PubMed

    Eby, Jonathan M; Barse, Levi; Henning, Steven W; Rabelink, Martijn J W E; Klarquist, Jared; Gilbert, Emily R; Hammer, Adam M; Fernandez, Manuel F; Yung, Nathan; Khan, Safia; Miller, Hannah G; Kessler, Edward R; Garrett-Mayer, Elizabeth; Dilling, Daniel F; Hoeben, Rob C; Le Poole, I Caroline

    2017-01-01

    An immunotherapeutic strategy is discussed supporting anti-tumor activity toward malignancies overexpressing ganglioside D3. GD3 can be targeted by NKT cells when derived moieties are presented in the context of CD1d. NKT cells can support anti-tumor responses by secreting inflammatory cytokines and through cytotoxicity toward CD1d(+)GD3(+) tumors. To overexpress GD3, we generated expression vector DNA and an adenoviral vector encoding the enzyme responsible for generating GD3 from its ubiquitous precursor GM3. We show that DNA encoding α-N-acetyl-neuraminide α-2,8-sialyltransferase 1 (SIAT8) introduced by gene gun vaccination in vivo leads to overexpression of GD3 and delays tumor growth. Delayed tumor growth is dependent on CD1d expression by host immune cells, as shown in experiments engaging CD1d knockout mice. A trend toward greater NKT cell populations among tumor-infiltrating lymphocytes is associated with SIAT8 vaccination. A single adenoviral vaccination introduces anti-tumor activity similarly to repeated vaccination with naked DNA. Here, greater NKT tumor infiltrates were accompanied by marked overexpression of IL-17 in the tumor, later switching to IL-4. Our results suggest that a single intramuscular adenoviral vaccination introduces overexpression of GD3 by antigen-presenting cells at the injection site, recruiting NKT cells that provide an inflammatory anti-tumor environment. We propose adenoviral SIAT8 (AdV-SIAT8) can slow the growth of GD3 expressing tumors in patients.

  1. Flow-cytometric monitoring of disease-associated expression of 9-O-acetylated sialoglycoproteins in combination with known CD antigens, as an index for MRD in children with acute lymphoblastic leukaemia: a two-year longitudinal follow-up study

    PubMed Central

    Chowdhury, Suchandra; Bandyopadhyay, Suman; Mandal, Chandan; Chandra, Sarmila; Mandal, Chitra

    2008-01-01

    Background Over expression of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs, abbreviated as OAcSGP) has been demonstrated as a disease-associated antigen on the lymphoblasts of childhood acute lymphoblastic leukaemia (ALL). Achatinin-H, a lectin, has selective affinity towards terminal 9-O-acetylated sialic acids-α2-6-Nacetylated galactosamine. Exploring this affinity, enhanced expression of OAcSGP was observed, at the onset of disease, followed by its decrease with chemotherapy and reappearance with relapse. In spite of treatment, patients retain the diseased cells referred to as minimal residual disease (MRD) responsible for relapse. Our aim was to select a suitable template by using the differential expression of OAcSGP along with other known CD antigens to monitor MRD in peripheral blood (PB) and bone marrow (BM) of Indian patients with B- or T-ALL during treatment and correlate it with the disease status. Methods A two-year longitudinal follow-up study was done with 109 patients from the onset of the disease till the end of chemotherapy, treated under MCP841protocol. Paired samples of PB (n = 1667) and BM (n = 999) were monitored by flow cytometry. Three templates selected for this investigation were OAcSGP+CD10+CD19+ or OAcSGP+CD34+CD19+ for B-ALL and OAcSGP+CD7+CD3+ for T-ALL. Results Using each template the level of MRD detection reached 0.01% for a patient in clinical remission (CR). 81.65% of the patients were in CR during these two years while the remaining relapsed. Failure in early clearance of lymphoblasts, as indicated by higher MRD, implied an elevated risk of relapse. Soaring MRD during the chemotherapeutic regimen predicted clinical relapse, at least a month before medical manifestation. Irrespective of B- or T-lineage ALL, the MRD in PB and BM correlated well. Conclusion A range of MRD values can be predicted for the patients in CR, irrespective of their lineage, being 0.03 ± 0.01% (PB) and 0.05 ± 0.015% (BM). These patients may not be

  2. Luminescent properties of Tb 3+ and Gd 3+ ions doped aluminosilicate oxyfluoride glasses

    NASA Astrophysics Data System (ADS)

    Zuo, Chenggang; Lu, Anxian; Zhu, Ligang; Zhou, Zhihua; Long, Woyun

    2011-11-01

    Tb 3+ and Gd 3+ ions doped lithium-barium-aluminosilicate oxyfluoride glasses have been prepared. The transmission, emission and excitation spectra were measured. It has been found that those Tb 3+-doped lithium-barium-aluminosilicate oxyfluoride glasses exhibit good UV-excited luminescence. The luminescence intensity of Tb 3+ ion increases for those (Tb 3+, Gd 3+)-codoped glasses. Energy transfer process from Gd 3+ ion to Tb 3+ ion is indicated.

  3. Involvement of gangliosides in the process of Cbp/PAG phosphorylation by Lyn in developing cerebellar growth cones.

    PubMed

    Sekino-Suzuki, Naoko; Yuyama, Kohei; Miki, Toshiaki; Kaneda, Mizuho; Suzuki, Hidenori; Yamamoto, Naomasa; Yamamoto, Tadashi; Oneyama, Chitose; Okada, Masato; Kasahara, Kohji

    2013-02-01

    The association of gangliosides with specific proteins in the central nervous system was examined by coimmunoprecipitation with an anti-ganglioside antibody. The monoclonal antibody to the ganglioside GD3 (R24) immunoprecipitated the Csk (C-terminal src kinase)-binding protein (Cbp). Sucrose density gradient analysis showed that Cbp of rat cerebellum was detected in detergent-resistant membrane (DRM) raft fractions. R24 treatment of the rat primary cerebellar cultures induced Lyn activation and tyrosine phosphorylation of Cbp. Treatment with anti-ganglioside GD1b antibody also induced tyrosine phosphorylation. Furthermore, over-expressions of Lyn and Cbp in Chinese hamster ovary (CHO) cells resulted in tyrosine 314 phosphorylation of Cbp, which indicates that Cbp is a substrate for Lyn. Immunoblotting analysis showed that the active form of Lyn and the Tyr314-phosphorylated form of Cbp were highly accumulated in the DRM raft fraction prepared from the developing cerebellum compared with the DRM raft fraction of the adult one. In addition, Lyn and the Tyr314-phosphorylated Cbp were highly concentrated in the growth cone fraction prepared from the developing cerebellum. Immunoelectron microscopy showed that Cbp and GAP-43, a growth cone marker, are localized in the same vesicles of the growth cone fraction. These results suggest that Cbp functionally associates with gangliosides on growth cone rafts in developing cerebella. © 2012 International Society for Neurochemistry.

  4. New trends in ganglioside chemistry

    SciTech Connect

    Sonnino, S.; Ghidoni, R.; Gazzotti, G.; Acquotti, D.; Tettamanti, G.

    1988-01-01

    New methods have been developed for the preparation of highly purified gangliosides, homogeneous in the saccharide, long chain base, and fatty acid moieties and gangliosides carrying different kinds of labelled probes. Gangliosides, homogeneous in the oligosaccharide portion, were prepared by preparative normal phase HPLC on a Lichrosorb-NH-2 column, using a gradient of acetonitrile-phosphate buffer, pH 5.6, as solvent system. Each class of ganglioside (from monosialo- to tetrasialogangliosides) was then submitted to reversed phase HPLC on a preparative RP-8 column, using acetonitrile-5 mM phosphate buffer, pH 7, as solvent system, to obtain gangliosides homogeneous in the long chain base moiety. Gangliosides containing C18 and C20 sphinganine were prepared by catalytic hydrogenation of the corresponding unsaturated gangliosides. GM1 with homogeneous acyl chain was prepared by alkaline hydrolysis in the presence of tetramethylammonium hydroxide, followed by re-N-acylation, carried out in the presence of dimethylaminopropyl, ethylcarbodiimide and natural fatty acids, or of mixed anhydride of ethylchloroformate and 14C-stearic acid, and re-N-acetylation performed with acetic anhydride or labelled acetic anhydride. The GM1 derivative, de-acetylated at the level of sialic acid, also produced by alkaline treatment of GM1, was submitted to re-N-acetylation with 14C-acetic anhydride to produce specifically 14C-labelled GM1. Re-N-acylation was carried out a) in the presence of dimethylaminopropyl, ethylcarbodiimide and natural fatty acids, b) with mixed anhydride of ethylchloroformate and 14C-stearic acid. After re-N-acylations, re-N-acetylation was performed with acetic anhydride or labelled acetic anhydride. 53 references.

  5. Endogenous immune response to gangliosides in patients with confined prostate cancer.

    PubMed

    Ravindranath, Mepur H; Muthugounder, Sakunthala; Presser, Naftali; Ye, Xing; Brosman, Stanley; Morton, Donald L

    2005-09-01

    Our study investigated whether endogenous IgM antibodies to gangliosides occur in patients with early stages of prostate cancer (CaP) patients, after defining ganglioside profiles of CaP cell lines. Immune and resorcinol staining detected the presence of gangliosides GM3, GM2, GD3, GD2 and GD1a but not GM1a, GD1b or GT1b in the extracts of normal prostatic epithelial cells (PrEC) and neoplastic androgen-insensitive (PC-3, DU145) and -sensitive (LNCaP-FGC and LNCaP-FGC-10) CaP cells. Using a sensitive ELISA, developed and validated in our laboratory, the titers of IgM against 8 gangliosides from sera of patients with benign prostatic hyperplasia (BPH) (n = 11), organ-confined (T1/T2, n = 36) and unconfined (T3/T4, n = 27) CaP and age-matched healthy men (n = 11) were determined double-blinded. Using ANOVA and Fisher's least significant difference (LSD) methods, the log-titers among different groups were compared. CaP patients differed from healthy and BPH patients in increased titers against GD1a and decreased titers against GD3. Titers of antibodies to other gangliosides exhibited no difference between CaP patients and others. The specific augmentation of anti-GD1a IgM in patients with organ-confined CaP (stage T1/T2) but not in patients with unconfined CaP (stage T3/T4) or BPH or in healthy controls is striking. This finding together with identification of GD1a as a major ganglioside in CaP cell lines and with the accruing studies on the immunosuppressive nature of GD1a indicates that augmentation of anti-GD1a IgM in confined CaP may signify an early endogenous immune response to eliminate a "danger signal" from tumor microenvironment and circulation.

  6. Tumor gangliosides accelerate murine tumor angiogenesis.

    PubMed

    Liu, Yihui; Wondimu, Assefa; Yan, Su; Bobb, Daniel; Ladisch, Stephan

    2014-07-01

    Tumor cells shed gangliosides and populate their microenvironment with these biologically active membrane glycosphingolipids. In vitro, ganglioside enrichment amplifies receptor tyrosine kinase signaling and activation of vascular endothelial cells. However, a long-standing question is whether in the actual microenvironment of a neoplasm, in vivo, tumor cell ganglioside shedding stimulates angiogenesis. Here we tested the hypothesis that tumor gangliosides have a critical proangiogenic role in vivo using novel murine tumor cells, GM3synthase/GM2synthase double knockout (DKO) cells, genetically completely incapable of ganglioside synthesis and impaired in tumor growth versus wild-type (WT) ganglioside-rich cells. We studied angiogenesis during tumor formation by these ganglioside-depleted cells, quantifying vessel formation, angiogenic factor production/release, and consequences of reconstitution with purified WT gangliosides. DKO cells formed virtually avascular tumors, much smaller than ganglioside-rich WT tumors and displaying a striking paucity of blood vessels, despite levels of VEGF and other angiogenic factors that were similar to those of WT cells. Transient enrichment of the ganglioside milieu of the DKO cell inoculum by adding purified WT gangliosides partially restored angiogenesis and tumor growth. We conclude that tumor gangliosides trigger robust angiogenesis important for tumor growth. Our findings suggest strategies to eliminate their synthesis and shedding by tumor cells should be pursued.

  7. Heterogeneity of gangliosides among T cell subsets.

    PubMed

    Inokuchi, Jin-ichi; Nagafuku, Masakazu; Ohno, Isao; Suzuki, Akemi

    2013-09-01

    Gangliosides are major components of highly organized membrane microdomains or rafts, yet little is known about the role of gangliosides in raft organization. This is also the case of gangliosides in TCR-mediated activation. Comprehensive structural analysis of gangliosides in the primary thymocytes and CD4(+) T and CD8(+) T cells was not achieved due to technical difficulties. We have found that CD8(+) T cells express very high levels of o-series gangliosides, but on the other hand, CD4(+) T cells preferably express a-series gangliosides. In the TCR-dependent activation, CD4(+) T cells selectively require a-series gangliosides, but CD8(+) T cells do require only o-series gangliosides but not a-series gangliosides. Ganglioside GM3 synthase-deficient mice lacking a-series gangliosides neither exhibited the TCR-dependent activation of CD4(+) T nor developed ovalbumin-induced allergic airway inflammation. These findings imply that the distinct expression pattern of ganglioside species in CD4(+) and CD8(+) T cells define the immune function of each T cell subset.

  8. Tumor gangliosides accelerate murine tumor angiogenesis

    PubMed Central

    Liu, Yihui; Wondimu, Assefa; Yan, Su; Bob, Daniel; Ladisch, Stephan

    2013-01-01

    Tumor cells shed gangliosides and populate their microenvironment with these biologically active membrane glycosphingolipids. In vitro, ganglioside enrichment amplifies receptor tyrosine kinase signaling and activation of vascular endothelial cells. However, a long-standing question is whether in the actual microenvironment of a neoplasm, in vivo, tumor cell ganglioside shedding stimulates angiogenesis. Here we tested the hypothesis that tumor gangliosides have a critical proangiogenic role in vivo using novel murine tumor cells (DKO) genetically completely incapable of ganglioside synthesis and impaired in tumor growth vs. wild-type (WT) ganglioside-rich cells. We studied angiogenesis during tumor formation by these ganglioside-depleted cells, quantifying vessel formation, angiogenic factor production/release, and consequences of reconstitution with purified WT gangliosides. DKO cells formed virtually avascular tumors, much smaller than ganglioside-rich WT tumors and displaying a striking paucity of blood vessels, despite levels of VEGF and other angiogenic factors that were similar to those of WT cells. Transient enrichment of the ganglioside milieu of the DKO cell inoculum by adding purified WT gangliosides partially restored angiogenesis and tumor growth. We conclude that tumor gangliosides trigger robust angiogenesis important for tumor growth. Our findings suggest strategies to eliminate their synthesis and shedding by tumor cells should be pursued. PMID:24165965

  9. Activation of human naïve Th cells increases surface expression of GD3 and induces neoexpression of GD2 that colocalize with TCR clusters.

    PubMed

    Villanueva-Cabello, Tania M; Mollicone, Rosella; Cruz-Muñoz, Mario E; López-Guerrero, Delia V; Martínez-Duncker, Iván

    2015-12-01

    CD4+ T helper lymphocytes (Th) orchestrate the immune response after their activation by antigen-presenting cells. Activation of naïve Th cells is reported to generate the reduction in surface epitopes of sialic acid (Sia) in α2,3 and α2,6 linkages. In this work, we report that in spite of this glycophenotype, anti-CD3/anti-CD28-activated purified human naïve Th cells show a significant increase in surface Sia, as assessed by metabolic labeling, compared with resting naïve Th cells, suggesting an increased flux of Sia toward Siaα2,8 glycoconjugates. To understand this increase as a result of ganglioside up-regulation, we observed that very early after activation, human naïve Th cells show an increased expression in surface GD3 and neoexpression of surface GD2 gangliosides, the latter clustering with the T cell receptor (TCR). Also, we report that in contrast to GM2/GD2 synthase null mice, lentiviral vector-mediated silencing of the GM2/GD2 synthase in activated human naïve Th cells reduced efficient TCR clustering and downstream signaling, as assessed by proliferation assays and IL-2 and IL-2R expression, pointing to an important role of this enzyme in activation of human naive Th cells. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Quantitative analysis of gangliosides in bovine milk and colostrum-based dairy products by ultrahigh performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Lee, Hyeyoung; German, J Bruce; Kjelden, Randy; Lebrilla, Carlito B; Barile, Daniela

    2013-10-09

    Milk gangliosides have gained considerable attention because they participate in diverse biological processes, including neural development, pathogen binding, and activation of the immune system. Herein, we present a quantitative measurement of the gangliosides present in bovine milk and other dairy products and byproducts. Ultrahigh performance liquid chromatography separation was used for high-throughput analysis and achieved a short running time without sacrificing chromatographic resolution. Dynamic multiple reaction monitoring was conducted for 12 transitions for GM3 and 12 transitions for GD3. Transitions to sialic acid fragments (m/z 290.1) were chosen for the quantitation. There was a considerable amount of gangliosides in day 2 milk (GM3, 0.98 mg/L; GD3, 15.2 mg/L) which dramatically decreased at day 15 and day 90. GM3 and GD3 were also analyzed in pooled colostrum, colostrum cream, colostrum butter, and colostrum buttermilk. The separation and analytical approaches here proposed could be integrated into the dairy industry processing adding value to side-streams.

  11. Ganglioside GD2 in reception and transduction of cell death signal in tumor cells

    PubMed Central

    2014-01-01

    Background Ganglioside GD2 is expressed on plasma membranes of various types of malignant cells. One of the most promising approaches for cancer immunotherapy is the treatment with monoclonal antibodies recognizing tumor-associated markers such as ganglioside GD2. It is considered that major mechanisms of anticancer activity of anti-GD2 antibodies are complement-dependent cytotoxicity and/or antibody-mediated cellular cytotoxicity. At the same time, several studies suggested that anti-GD2 antibodies are capable of direct induction of cell death of number of tumor cell lines, but it has not been investigated in details. In this study we investigated the functional role of ganglioside GD2 in the induction of cell death of multiple tumor cell lines by using GD2-specific monoclonal antibodies. Methods Expression of GD2 on different tumor cell lines was analyzed by flow cytometry using anti-GD2 antibodies. By using HPTLC followed by densitometric analysis we measured the amount of ganglioside GD2 in total ganglioside fractions isolated from tumor cell lines. An MTT assay was performed to assess viability of GD2-positive and -negative tumor cell lines treated with anti-GD2 mAbs. Cross-reactivity of anti-GD2 mAbs with other gangliosides or other surface molecules was investigated by ELISA and flow cytometry. Inhibition of GD2 expression was achieved by using of inhibitor for ganglioside synthesis PDMP and/or siRNA for GM2/GD2 and GD3 synthases. Results Anti-GD2 mAbs effectively induced non-classical cell death that combined features of both apoptosis and necrosis in GD2-positive tumor cells and did not affect GD2-negative tumors. Anti-GD2 mAbs directly induced cell death, which included alteration of mitochondrial membrane potential, induction of apoptotic volume decrease and cell membrane permeability. This cytotoxic effect was mediated exclusively by specific binding of anti-GD2 antibodies with ganglioside GD2 but not with other molecules. Moreover, the level of GD2

  12. Ganglioside GD2 in reception and transduction of cell death signal in tumor cells.

    PubMed

    Doronin, Igor I; Vishnyakova, Polina A; Kholodenko, Irina V; Ponomarev, Eugene D; Ryazantsev, Dmitry Y; Molotkovskaya, Irina M; Kholodenko, Roman V

    2014-04-28

    Ganglioside GD2 is expressed on plasma membranes of various types of malignant cells. One of the most promising approaches for cancer immunotherapy is the treatment with monoclonal antibodies recognizing tumor-associated markers such as ganglioside GD2. It is considered that major mechanisms of anticancer activity of anti-GD2 antibodies are complement-dependent cytotoxicity and/or antibody-mediated cellular cytotoxicity. At the same time, several studies suggested that anti-GD2 antibodies are capable of direct induction of cell death of number of tumor cell lines, but it has not been investigated in details. In this study we investigated the functional role of ganglioside GD2 in the induction of cell death of multiple tumor cell lines by using GD2-specific monoclonal antibodies. Expression of GD2 on different tumor cell lines was analyzed by flow cytometry using anti-GD2 antibodies. By using HPTLC followed by densitometric analysis we measured the amount of ganglioside GD2 in total ganglioside fractions isolated from tumor cell lines. An MTT assay was performed to assess viability of GD2-positive and -negative tumor cell lines treated with anti-GD2 mAbs. Cross-reactivity of anti-GD2 mAbs with other gangliosides or other surface molecules was investigated by ELISA and flow cytometry. Inhibition of GD2 expression was achieved by using of inhibitor for ganglioside synthesis PDMP and/or siRNA for GM2/GD2 and GD3 synthases. Anti-GD2 mAbs effectively induced non-classical cell death that combined features of both apoptosis and necrosis in GD2-positive tumor cells and did not affect GD2-negative tumors. Anti-GD2 mAbs directly induced cell death, which included alteration of mitochondrial membrane potential, induction of apoptotic volume decrease and cell membrane permeability. This cytotoxic effect was mediated exclusively by specific binding of anti-GD2 antibodies with ganglioside GD2 but not with other molecules. Moreover, the level of GD2 expression correlated with

  13. Ganglioside accumulation in activated glia in the developing brain: comparison between WT and GalNAcT KO mice.

    PubMed

    Saito, Mariko; Wu, Gusheng; Hui, Maria; Masiello, Kurt; Dobrenis, Kostantin; Ledeen, Robert W; Saito, Mitsuo

    2015-08-01

    Our previous studies have shown accumulation of GM2 ganglioside during ethanol-induced neurodegeneration in the developing brain, and GM2 elevation has also been reported in other brain injuries and neurodegenerative diseases. Using GM2/GD2 synthase KO mice lacking GM2/GD2 and downstream gangliosides, the current study explored the significance of GM2 elevation in WT mice. Immunohistochemical studies indicated that ethanol-induced acute neurodegeneration in postnatal day 7 (P7) WT mice was associated with GM2 accumulation in the late endosomes/lysosomes of both phagocytic microglia and increased glial fibrillary acidic protein (GFAP)-positive astrocytes. However, in KO mice, although ethanol induced robust neurodegeneration and accumulation of GD3 and GM3 in the late endosomes/lysosomes of phagocytic microglia, it did not increase the number of GFAP-positive astrocytes, and the accumulation of GD3/GM3 in astrocytes was minimal. Not only ethanol, but also DMSO, induced GM2 elevation in activated microglia and astrocytes along with neurodegeneration in P7 WT mice, while lipopolysaccharide, which did not induce significant neurodegeneration, caused GM2 accumulation mainly in lysosomes of activated astrocytes. Thus, GM2 elevation is associated with activation of microglia and astrocytes in the injured developing brain, and GM2, GD2, or other downstream gangliosides may regulate astroglial responses in ethanol-induced neurodegeneration.

  14. Ganglioside accumulation in activated glia in the developing brain: comparison between WT and GalNAcT KO mice

    PubMed Central

    Saito, Mariko; Wu, Gusheng; Hui, Maria; Masiello, Kurt; Dobrenis, Kostantin; Ledeen, Robert W.; Saito, Mitsuo

    2015-01-01

    Our previous studies have shown accumulation of GM2 ganglioside during ethanol-induced neurodegeneration in the developing brain, and GM2 elevation has also been reported in other brain injuries and neurodegenerative diseases. Using GM2/GD2 synthase KO mice lacking GM2/GD2 and downstream gangliosides, the current study explored the significance of GM2 elevation in WT mice. Immunohistochemical studies indicated that ethanol-induced acute neurodegeneration in postnatal day 7 (P7) WT mice was associated with GM2 accumulation in the late endosomes/lysosomes of both phagocytic microglia and increased glial fibrillary acidic protein (GFAP)-positive astrocytes. However, in KO mice, although ethanol induced robust neurodegeneration and accumulation of GD3 and GM3 in the late endosomes/lysosomes of phagocytic microglia, it did not increase the number of GFAP-positive astrocytes, and the accumulation of GD3/GM3 in astrocytes was minimal. Not only ethanol, but also DMSO, induced GM2 elevation in activated microglia and astrocytes along with neurodegeneration in P7 WT mice, while lipopolysaccharide, which did not induce significant neurodegeneration, caused GM2 accumulation mainly in lysosomes of activated astrocytes. Thus, GM2 elevation is associated with activation of microglia and astrocytes in the injured developing brain, and GM2, GD2, or other downstream gangliosides may regulate astroglial responses in ethanol-induced neurodegeneration. PMID:26063460

  15. Ganglioside GM3 is essential for the structural integrity and function of cochlear hair cells.

    PubMed

    Yoshikawa, Misato; Go, Shinji; Suzuki, Shun-ichi; Suzuki, Akemi; Katori, Yukio; Morlet, Thierry; Gottlieb, Steven M; Fujiwara, Michihiro; Iwasaki, Katsunori; Strauss, Kevin A; Inokuchi, Jin-ichi

    2015-05-15

    GM3 synthase (ST3GAL5) is the first biosynthetic enzyme of a- and b-series gangliosides. Patients with GM3 synthase deficiency suffer severe neurological disability and deafness. Eight children (ages 4.1 ± 2.3 years) homozygous for ST3GAL5 c.694C>T had no detectable GM3 (a-series) or GD3 (b-series) in plasma. Their auditory function was characterized by the absence of middle ear muscle reflexes, distortion product otoacoustic emissions and cochlear microphonics, as well as abnormal auditory brainstem responses and cortical auditory-evoked potentials. In St3gal5(-/-) mice, stereocilia of outer hair cells showed signs of degeneration as early as postnatal Day 3 (P3); thereafter, blebs devoid of actin or tubulin appeared at the region of vestigial kinocilia, suggesting impaired vesicular trafficking. Stereocilia of St3gal5(-/-) inner hair cells were fused by P17, and protein tyrosine phosphatase receptor Q, normally linked to myosin VI at the tapered base of stereocilia, was maldistributed along the cell membrane. B4galnt1(-/-) (GM2 synthase-deficient) mice expressing only GM3 and GD3 gangliosides had normal auditory structure and function. Thus, GM3-dependent membrane microdomains might be essential for the proper organization and maintenance of stereocilia in auditory hair cells. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Ganglioside GM3 is essential for the structural integrity and function of cochlear hair cells

    PubMed Central

    Yoshikawa, Misato; Go, Shinji; Suzuki, Shun-ichi; Suzuki, Akemi; Katori, Yukio; Morlet, Thierry; Gottlieb, Steven M.; Fujiwara, Michihiro; Iwasaki, Katsunori; Strauss, Kevin A.; Inokuchi, Jin-ichi

    2015-01-01

    GM3 synthase (ST3GAL5) is the first biosynthetic enzyme of a- and b-series gangliosides. Patients with GM3 synthase deficiency suffer severe neurological disability and deafness. Eight children (ages 4.1 ± 2.3 years) homozygous for ST3GAL5 c.694C>T had no detectable GM3 (a-series) or GD3 (b-series) in plasma. Their auditory function was characterized by the absence of middle ear muscle reflexes, distortion product otoacoustic emissions and cochlear microphonics, as well as abnormal auditory brainstem responses and cortical auditory-evoked potentials. In St3gal5−/− mice, stereocilia of outer hair cells showed signs of degeneration as early as postnatal Day 3 (P3); thereafter, blebs devoid of actin or tubulin appeared at the region of vestigial kinocilia, suggesting impaired vesicular trafficking. Stereocilia of St3gal5−/− inner hair cells were fused by P17, and protein tyrosine phosphatase receptor Q, normally linked to myosin VI at the tapered base of stereocilia, was maldistributed along the cell membrane. B4galnt1−/− (GM2 synthase-deficient) mice expressing only GM3 and GD3 gangliosides had normal auditory structure and function. Thus, GM3-dependent membrane microdomains might be essential for the proper organization and maintenance of stereocilia in auditory hair cells. PMID:25652401

  17. Rapid Profiling of Bovine and Human Milk Gangliosides by Matrix-Assisted Laser Desorption/Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

    PubMed Central

    Lee, Hyeyoung; An, Hyun Joo; Lerno, Larry A.; German, J. Bruce; Lebrilla, Carlito B.

    2010-01-01

    Gangliosides are anionic glycosphingolipids widely distributed in vertebrate tissues and fluids. Their structural and quantitative expression patterns depend on phylogeny and are distinct down to the species level. In milk, gangliosides are exclusively associated with the milk fat globule membrane. They may participate in diverse biological processes but more specifically to host-pathogen interactions. However, due to the molecular complexities, the analysis needs extensive sample preparation, chromatographic separation, and even chemical reaction, which makes the process very complex and time-consuming. Here, we describe a rapid profiling method for bovine and human milk gangliosides employing matrix-assisted desorption/ionization (MALDI) Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS). Prior to the analyses of biological samples, milk ganglioside standards GM3 and GD3 fractions were first analyzed in order to validate this method. High mass accuracy and high resolution obtained from MALDI FTICR MS allow for the confident assignment of chain length and degree of unsaturation of the ceramide. For the structural elucidation, tandem mass spectrometry (MS/MS), specifically as collision-induced dissociation (CID) and infrared multiphoton dissociation (IRMPD) were employed. Complex ganglioside mixtures from bovine and human milk were further analyzed with this method. The samples were prepared by two consecutive chloroform/methanol extraction and solid phase extraction. We observed a number of differences between bovine milk and human milk. The common gangliosides in bovine and human milk are NeuAc-NeuAc-Hex-Hex-Cer (GD3) and NeuAc-Hex-Hex-Cer (GM3); whereas, the ion intensities of ganglioside species are different between two milk samples. Kendrick mass defect plot yields grouping of ganglioside peaks according to their structural similarities. Gangliosides were further probed by tandem MS to confirm the compositional and structural assignments

  18. External electric field effects on Schottky barrier at Gd3N@C80/Au interface

    NASA Astrophysics Data System (ADS)

    Onishi, Koichi; Nakashima, Fumihiro; Jin, Ge; Eto, Daichi; Hattori, Hayami; Miyoshi, Noriko; Kirimoto, Kenta; Sun, Yong

    2017-08-01

    The effects of the external electric field on the height of the Schottky barrier at the Gd3N@C80/Au interface were studied by measuring current-voltage characteristics at various temperatures from 200 K to 450 K. The Gd3N@C80 sample with the conduction/forbidden/valence energy band structure had a face-centered cubic crystal structure with the average grain size of several nanometers. The height of the Gd3N@C80/Au Schottky barrier was confirmed to be 400 meV at a low electric field at room temperature. Moreover, the height decreases with the increasing external electric field through a change of permittivity in the Gd3N@C80 sample due to a polarization of the [Gd3] 9 +-[N3 -+("separators="|C80 ) 6 -] dipoles in the Gd3N@C80 molecule. The field-dependence of the barrier height can be described using a power math function of the electric field strength. The results of the field-dependent barrier height indicate that the reduction in the Schottky barrier is due to an image force effect of the transport charge carrier at the Gd3N@C80/Au interface.

  19. Ganglioside and Non-ganglioside Mediated Host Responses to the Mouse Polyomavirus

    PubMed Central

    Velupillai, Palanivel; Castle, Sherry; Garcea, Robert L.; Benjamin, Thomas

    2015-01-01

    Gangliosides serve as receptors for internalization and infection by members of the polyomavirus family. Specificity is determined by recognition of carbohydrate moieties on the ganglioside by the major viral capsid protein VP1. For the mouse polyomavirus (MuPyV), gangliosides with terminal sialic acids in specific linkages are essential. Although many biochemical and cell culture experiments have implicated gangliosides as MuPyV receptions, the role of gangliosides in the MuPyV-infected mouse has not been investigated. Here we report results of studies using ganglioside-deficient mice and derived cell lines. Knockout mice lacking complex gangliosides were completely resistant to the cytolytic and pathogenic effects of the virus. Embryo fibroblasts from these mice were likewise resistant to infection, and supplementation with specific gangliosides restored infectibility. Although lacking receptors for viral infection, cells from ganglioside-deficient mice retained the ability to respond to the virus. Ganglioside-deficient fibroblasts responded rapidly to virus exposure with a transient induction of c-fos as an early manifestation of a mitogenic response. Additionally, splenocytes from ganglioside-deficient mice responded to MuPyV by secretion of IL-12, previously recognized as a key mediator of the innate immune response. Thus, while gangliosides are essential for infection in the animal, gangliosides are not required for mitogenic responses and innate immune responses to the virus. PMID:26474471

  20. Structural analysis of brain ganglioside acetylation patterns in mice with altered ganglioside biosynthesis.

    PubMed

    Mlinac, Kristina; Fabris, Dragana; Vukelić, Zeljka; Rožman, Marko; Heffer, Marija; Bognar, Svjetlana Kalanj

    2013-12-15

    Gangliosides are sialylated membrane glycosphingolipids especially abundant in mammalian brain tissue. Sialic acid O-acetylation is one of the most common structural modifications of gangliosides which considerably influences their chemical properties. In this study, gangliosides extracted from brain tissue of mice with altered ganglioside biosynthesis (St8sia1 null and B4galnt1 null mice) were structurally characterized and their acetylation pattern was analyzed. Extracted native and alkali-treated gangliosides were resolved by high performance thin layer chromatography. Ganglioside mixtures as well as separated individual ganglioside fractions were further analyzed by tandem mass spectrometry. Several O-acetylated brain ganglioside species were found in knockout mice, not present in the wild-type mice. To the best of our knowledge this is the first report on the presence of O-acetylated GD1a in St8sia1 null mice and O-acetylated GM3 species in B4galnt1 null mice. In addition, much higher diversity of abnormally accumulated brain ganglioside species regarding the structure of ceramide portion was observed in knockout versus wild-type mice. Obtained findings indicate that the diversity of brain ganglioside structures as well as acetylation patterns in mice with altered ganglioside biosynthesis, is even higher than previously reported. Further investigation is needed in order to explore the effects of acetylation on ganglioside interactions with other molecules and consequently the physiological role of acetylated ganglioside species. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Gangliosides induce autophagic cell death in astrocytes

    PubMed Central

    Hwang, Jaegyu; Lee, Shinrye; Lee, Jung Tae; Kwon, Taeg Kyu; Kim, Deok Ryong; Kim, Ho; Park, Hae-Chul; Suk, Kyoungho

    2010-01-01

    Background and purpose: Gangliosides, sialic acid-containing glycosphingolipids, abundant in brain, are involved in neuronal function and disease, but the precise molecular mechanisms underlying their physiological or pathological activities are poorly understood. In this study, the pathological role of gangliosides in the extracellular milieu with respect to glial cell death and lipid raft/membrane disruption was investigated. Experimental approach: We determined the effect of gangliosides on astrocyte death or survival using primary astrocyte cultures and astrocytoma/glioma cell lines as a model. Signalling pathways of ganglioside-induced autophagic cell death of astrocytes were examined using pharmacological inhibitors and biochemical and genetic assays. Key results: Gangliosides induced autophagic cell death in based on the following observations. Incubation of the cells with a mixture of gangliosides increased a punctate distribution of fluorescently labelled microtubule-associated protein 1 light chain 3 (GFP-LC3), the ratio of LC3-II/LC3-I and LC3 flux. Gangliosides also increased the formation of autophagic vacuoles as revealed by monodansylcadaverine staining. Ganglioside-induced cell death was inhibited by either a knockdown of beclin-1/Atg-6 or Atg-7 gene expression or by 3-methyladenine, an inhibitor of autophagy. Reactive oxygen species (ROS) were involved in ganglioside-induced autophagic cell death of astrocytes, because gangliosides induced ROS production and ROS scavengers decreased autophagic cell death. In addition, lipid rafts played an important role in ganglioside-induced astrocyte death. Conclusions and implications: Gangliosides released under pathological conditions may induce autophagic cell death of astrocytes, identifying a neuropathological role for gangliosides. PMID:20067473

  2. Differentiation of oligodendrocytes cultured from developing rat brain is enhanced by exogenous GM3 ganglioside.

    PubMed

    Yim, S H; Farrer, R G; Hammer, J A; Yavin, E; Quarles, R H

    1994-06-15

    Cultures consisting primarily of O-2A progenitor cells and immature oligodendrocytes with a few microglia and astrocytes were obtained by shaking primary cultures from neonatal rat brain after 12-14 days in vitro. Addition of 50 micrograms/ml exogenous Neu-NAc alpha 2-3Gal beta 1-4Glc beta 1-1'ceramide (GM3 ganglioside) to the cultures resulted in an increase in the number and thickness of cell processes that stained intensely for sulfatide and galactocerebroside (galC) in comparison to control cultures without added GM3. The treated cultures also contained fewer astrocytes than control cultures as revealed by immunostaining for glial fibrillary acidic protein (GFAP). Cells that immunostained for both GFAP and sulfatide/galC were very rare in control cultures but were frequently seen in the GM3-treated cultures, suggesting that these may represent cells changing their direction of differentiation away from type II astrocytes toward oligodendrocytes under the influence of GM3. These effects on the developing rat oligodendrocytes were specific for GM3 ganglioside and were not produced by adding GM1, GM2, GD3, or GD1a to the cultures. Lactosyl ceramide and neuraminyl lactose were also ineffective. When control cultures were initially plated on polylysine and incubated with [14C]galactose, GD3 was the principal labeled ganglioside. However, as the control cells differentiated over time in culture without the addition of exogenous GM3 and produced increasing amounts of myelin-related components, the incorporation of [14C]galactose into endogenous GM3 increased to become the predominant labeled ganglioside by 6 days after plating. Metabolic labeling of the GM3-treated oligodendrocytes with [14C]galactose revealed increased incorporation into galC and sulfatide in comparison to control cultures, but a decreased labeling of endogenous GM3. Similarly, incorporation of an amino acid precursor into the myelin-associated glycoprotein (MAG) was increased by GM3 treatment, but

  3. A new liquid chromatography/tandem mass spectrometry method for quantification of gangliosides in human plasma.

    PubMed

    Huang, Qianyang; Zhou, Xiang; Liu, Danting; Xin, Baozhong; Cechner, Karen; Wang, Heng; Zhou, Aimin

    2014-06-15

    Gangliosides are a family of glycosphingolipids characterized by mono- or polysialic acid-containing oligosaccharides linked through 1,3- and 1,4-β glycosidic bonds with subtle differences in structure that are abundantly present in the central nervous systems of many living organisms. Their cellular surface expression and physiological malfunction are believed to be pathologically implicated in considerable neurological disorders, including Alzheimer and Parkinson diseases. Recently, studies have tentatively elucidated that mental retardation or physical stagnation deteriorates as the physiological profile of gangliosides becomes progressively and distinctively abnormal during the development of these typical neurodegenerative syndromes. In this work, a reverse-phase liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay using standard addition calibration for determination of GM2, GM3, GD2, and GD3 in human plasma has been developed and validated. The analytes and internal standard were extracted from human plasma using a simple protein precipitation procedure. Then the samples were analyzed by reverse-phase ultra-performance liquid chromatography (UPLC)/MS/MS interfaced to mass spectrometry with electrospray ionization using a multiple reaction monitoring mode to obtain superior sensitivity and specificity. This assay was validated for extraction recovery, calibration linearity, precision, and accuracy. Our quick and sensitive method can be applied to monitor ganglioside levels in plasma from normal people and neurodegenerative patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Ganglioside mimicry and peripheral nerve disease.

    PubMed

    Yuki, Nobuhiro

    2007-06-01

    Four criteria must be satisfied to conclude that a given microorganism causes Guillain-Barré (GBS) or Fisher (FS) syndrome associated with anti-ganglioside antibodies: (1) an epidemiological association between the infecting microbe and GBS or FS; (2) isolation in the acute progressive phase of illness of that microorganism from GBS or FS patients with associated anti-ganglioside IgG antibodies; (3) identification of a microbial ganglioside mimic; and (4) a GBS or FS with associated anti-ganglioside antibodies model produced by sensitization with the microbe itself or its component, as well as with ganglioside. Campylobacter jejuni is a definitive causative microorganism of acute motor axonal neuropathy and may cause FS and related conditions. Haemophilus influenzae and Mycoplasma pneumoniae are possible causative microorganisms of acute motor axonal neuropathy or FS. Acute and chronic inflammatory demyelinating polyneuropathies may be produced by mechanisms other than ganglioside mimicry.

  5. Improved luminescence of CaWO4:Eu3+ microspheres by codoping Gd3+

    NASA Astrophysics Data System (ADS)

    Chen, Guiqiang; Wang, Fengli; Ji, Wenchao; Liu, Yanxia; Zhang, Xiao

    2016-02-01

    CaWO4:Eu3+/Gd3+ samples have been synthesized through a hydrothermal process with the assistant of trisodium citrate. The phase and morphology of samples have been characterized by XRD, FTIR, SEM and TEM. The XRD results indicate that the samples have the pure scheelite phase. The SEM and TEM images show that the samples are microspheres containing lots of nanoparticles. The luminescent properties of CaWO4:Eu3+/Gd3+ samples also have been measured. Under the excitation at 278 nm, CaWO4:Eu3+/Gd3+ samples show characteristic emission bands originating from the 5D0 → 7Fj (j = 1, 2, 3 and 4) transitions of Eu3+ ions. The codoping Gd3+ ions can improve the emission intensity highly. Also, the samples show good thermal stability.

  6. Surface enhanced Raman scattering of amino acids assisted by gold nanoparticles and Gd(3+) ions.

    PubMed

    López-Neira, Juan Pablo; Galicia-Hernández, José Mario; Reyes-Coronado, Alejandro; Pérez, Elías; Castillo-Rivera, Francisco

    2015-05-07

    The surface enhanced raman scattering (SERS) signal from the l-tyrosine (tyr) molecule adsorbed on gold nanoparticles (Au-tyr) is compared with the SERS signal assisted by the presence of gadolinium ions (Gd(3+)) coordinated with the Au-tyr system. An enhancement factor of the SERS signal in the presence of Gd(3+) ions was ∼5 times higher than that produced by l-tyrosine adsorbed on gold nanoparticles. The enhancement of the SERS signal can be attributed to a corresponding increase in the local electric field due to the presence of Gd(3+) ions in the vicinity of a gold dimer configuration. This scenario was confirmed by solving numerically Maxwell equations, showing an increase of 1 order of magnitude in the local electric scattered field when the Gd(3+) ion is located in between a gold dimer compared with naked gold nanoparticles.

  7. THE ZEEMAN SPECTRA OF Gd3+ IN CaF2 AT CUBIC SITES.

    DTIC Science & Technology

    The octet S7/2 ground state Gd3 + is split only 0.149/cm by the cubic crystal field in CaF2 and is described at 11.3 kG by the projection quantum...conveniently described with reference to the 4-fold axes. The calculation of the dependence of the Zeeman spectra of Gd3 + in CaF2 at sites of cubic

  8. Effect of Gd3+ doping on structural and optical properties of ZnO nanocrystals

    NASA Astrophysics Data System (ADS)

    Mithal, Deepika; Kundu, Tapanendu

    2017-06-01

    To investigate the effect of rare earth ions on the excitation energy redistribution between the UV and visible photoluminescence, the Gd3+ doped ZnO nanocrystals prepared through Sol-Gel method were studied. Different structural characterizations and spectroscopic studies were carried out to establish a correlation between the structural effect and the photoluminescence. Our study indicates that the incorporation of Gd3+ in ZnO nanocrystals prepared through this synthesis takes place predominantly on the surface up to 0.18 mole fraction of Gd3+. This is manifested by the observed lattice contraction due to the presence of Gd3+ on the surface. This structural defect introduces various defects that modifies the photoluminescence properties. For these modifications in crystal system, the A1 symmetry phonon modes of wurtzite structure are found to be gradually more Raman active than the other modes as the Gd3+ concentration is increased while the E modes are suppressed. These doping induced modification of phonon spectrum strongly influences the exciton phonon coupling and thereby the photophysical properties. Resulting crystal imperfections strongly enhance the defect band luminescence. It is shown that energy transfer from selectively excited Gd3+ centers to surface states can be effectively exploited for the sensitization of defect band luminescence in various fields such as bio imaging, light emitting devices etc.

  9. Structural and magnetic properties of Gd3+ ion substituted magnesium ferrite nanopowders

    NASA Astrophysics Data System (ADS)

    Elkady, Ashraf S.; Hussein, Shaban I.; Rashad, Mohamed M.

    2015-07-01

    Nanocrystalline MgGdxFe2-xO4 powders (where x=0, 0.05, 0.1, 0.2, 0.25, 0.3) have been synthesized by the ethylene diamine tetraacetic acid (EDTA)-based sol-gel combustion method. X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, high resolution transmission electron microscopy (HRTEM) and vibrating sample magnetometer (VSM) were applied in order to study the effect of variation of Gd3+ ion substitution and its impact on crystal structure, crystallite size, lattice parameters, nanostructure and magnetic properties of the formed powders. XRD indicated that, after doping and calcination at 400 °C for 2 h, all samples have two spinel ferrite structures namely cubic and tetragonal phases, which are dependent on Gd3+ ion concentration. The cubic phase is found to increase with increasing the Gd3+ ion molar ratio up to 0.1, compared to pure MgFe2O4 and higher Gd3+ content samples. Indeed, with increasing Gd3+ ion, the crystallite size was almost unchanged whereas the lattice parameter was found to increase. FT-IR spectrum showed broadening of the ν2 band and the presence of another band in the range (465-470 cm-1) upon adding Gd3+ ion, which confirm the presence of Gd3+ ion in addition to Fe3+ ion at octahedral site. Besides, these bands were assigned to the formation of (Gd3+-O2-) complexes at B-sites. HRTEM images showed that the studied samples consist of nanocrystallites having average particle sizes around 9 nm for pure MgFe2O4 up to 27 and 42 nm for the Gd3+ ion substituted MgFe2O4 of molar ratio 0.05 and 0.30, respectively. An examination of the magnetic properties revealed an increase in saturation magnetization with increasing Gd concentration incorporation up to x=0.1, as a result of the change of cubic and tetragonal spinel ratio and lattice parameters. Meanwhile, the formed powders exhibited superparamagnetic characteristics. Therefore, such newly synthesized superparamagnetic nanoparticles, containing Gd3+ ion can be considered as a

  10. GM2 ganglioside and pyramidal neuron dendritogenesis.

    PubMed

    Walkley, S U; Siegel, D A; Dobrenis, K

    1995-11-01

    GM2 ganglioside, although scarce in normal adult brain, is the predominant ganglioside accumulating in several types of lysosomal disorders, most notably Tay-Sachs disease. Pyramidal neurons of cerebral cortex in Tay-Sachs, as well as many other types of neuronal storage disorders, are known to exhibit a phenomenon believed unique to storage disorders: growth of ectopic dendrites. Recent studies have shown that a common metabolic abnormality shared by storage diseases with ectopic dendrite growth is the abnormal accumulation of GM2 ganglioside. The correlation between increased levels of GM2 and the presence of ectopic dendrites has been found in both ganglioside and nonganglioside storage disorders, the latter including sphingomyelin-cholesterol lipidosis, mucopolysaccharidosis, and alpha-mannosidosis. Quantitative HPTLC analysis has shown that increases in GM2 occur in proportion to the incidence of ectopic dendrite growth, whereas other gangliosides, including GM1, lack similar increases. Immunocytochemical studies of all nonganglioside storage diseases which exhibit ectopic dendritogenesis have revealed heightened GM2 ganglioside-immunoreactivity in the cortical pyramidal cell population, whereas nerurons in normal adult brain exhibit little or no staining for this ganglioside. Further, studies examining disease development have consistently shown that accumulation of GM2 ganglioside precedes growth of ectopic dendrites, indicating that it is not simply occurring secondary to new membrane production. These findings have prompted an examination for a similar relationship between GM2 ganglioside and dendritogenesis in cortical neurons of normal developing brain. Results show that GM2 ganglioside-immunoreactivity is consistently elevated in immature neurons during the period when they are undergoing active dendritic initiation, but this staining diminishes dramatically as the dendritic trees of these cells mature. Collectively, these studies on diseased and normal

  11. Monosialyl Ganglioside GM3 Decreases Apolipoprotein B-100 Secretion in Liver Cells.

    PubMed

    Choi, Hyunju; Jin, Un-Ho; Kang, Sung-Koo; Abekura, Fukushi; Park, Jun-Young; Kwon, Kyung-Min; Suh, Seok-Jong; Cho, Seung-Hak; Ha, Ki-Tae; Lee, Young-Coon; Chung, Tae-Wook; Kim, Cheorl-Ho

    2017-08-01

    Some sialic acid-containing glycolipids are known to regulate development of atherosclerosis with accumulated plasma apolipoprotein B-100 (Apo-B)-containing lipoproteins, because Apo-B as an atherogenic apolipoprotein is assembled mainly in VLDL and LDL. Previously, we have elucidated that disialyl GD3 promotes the microsomal triglyceride transfer protein (MTP) gene expression and secretion of triglyceride (TG)-assembled ApoB, claiming the GD3 role in ApoB lipoprotein secretion in liver cells. In the synthetic pathway of gangliosides, GD3 is synthesized by addition of a sialic acid residue to GM3. Thus, there should be some regulatory links between GM3 and GD3. In this study, exogenous and endogenous monosialyl GM3 has been examined how GM3 plays a role in ApoB secretion in Chang liver cells in a view point of MTP and ApoB degradation in the same cells. The level of GM3 ganglioside in the GM3 synthase gene-transfected cells was increased in the cell extract, but not in the medium. In addition, GM3 synthase gene-transfected cells showed a diminished secretion of TG-enriched ApoB with a lower content of TG in the medium. Exogenous GM3 treatment for 24 h exerted a dose dependent inhibitory effect on ApoB secretion together with TG, while a liver-specific albumin was unchanged, indicating that GM3 effect is limited to ApoB secretion. GM3 decreased the mRNA level of MTP gene, too. ApoB protein assembly dysregulated by GM3 indicates the impaired ApoB secretion is caused by a proteasome-dependent pathway. Treatment with small interfering RNAs (siRNAs) decreased ApoB secretion, but GM3-specific antibody did not. These results indicate that plasma membrane associated GM3 inhibits ApoB secretion, lowers development of atherosclerosis by decreasing the secretion of TG-enriched ApoB containing lipoproteins, suggesting that GM3 is an inhibitor of ApoB and TG secretion in liver cells. J. Cell. Biochem. 118: 2168-2181, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley

  12. UVB-emitting Gd(3+)-activated M2O2S (where M = La, Y) for phototherapy lamp phosphors.

    PubMed

    Shinde, V V; Kunghatkar, R G; Dhoble, S J

    2015-12-01

    Gd(3+)-activated oxysulphide (M2O2S) may be used to study Photoluminescence (PL) properties with respect to phototherapy. Gd(3+)-activated phosphor materials are widely used for phototherapy lamps. The Gd(3+) ion gives characteristic Narrow-Band (NB) emissions, in particular in the ultraviolet (UV) light region, that are used to treat more than 50 types of skin diseases. In this paper, M2O2S oxysulphide doped with Gd(3+) was synthesized by the solid-state flux fusion method and its down conversion spectral properties were studied as a function of different Gd(3+) concentrations. The sample was characterized by X-ray Diffraction (XRD), Scanning Electron Microscope (SEM), Fourier Transform Infrared Spectroscopy (FT-IR), and PL and the crystal structure was also studied. The lanthanum oxysulphide (La2O2S)-activated Gd(3+) ion showed a sharp emission peak at 314 nm when excited at 275 nm excitation, whereas the yttrium oxysulphide (Y2O2S)-activated Gd(3+) ion showed a sharp emission at 316 nm when excited by 272 nm. The effect of concentration of the Gd(3+) ion on the luminescence properties of M2O2S:Gd(3+) phosphor was also studied. These phosphor materials activated with the Gd(3+) ion may be suitable for phototherapy lamps, which are used to treat many types of skin diseases such as psoriasis, vitiligo, or scleroderma. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Gangliosides of the Vertebrate Nervous System.

    PubMed

    Schnaar, Ronald L

    2016-08-14

    Gangliosides, sialylated glycosphingolipids, found on all vertebrate cells and tissues, are major molecular determinants on the surfaces of vertebrate nerve cells. Composed of a sialylated glycan attached to a ceramide lipid, the same four structures-GM1, GD1a, GD1b, and GT1b-represent the vast majority (>90%) of gangliosides in the brains of all mammals and birds. Primarily found on the outer surface of the plasma membrane with their glycans facing outward, gangliosides associate laterally with each other, sphingomyelin, cholesterol, and select proteins in lipid rafts-the dynamic functional subdomains of the plasma membrane. The functions of gangliosides in the human nervous system are revealed by congenital mutations in ganglioside biosynthetic genes. Mutations in ST3GAL5, which codes for an enzyme early in brain ganglioside biosynthesis, result in an early-onset seizure disorder with profound motor and cognitive decay, whereas mutations in B4GALNT1, a gene encoding a later step, result in hereditary spastic paraplegia accompanied by intellectual deficits. The molecular functions of brain gangliosides include regulation of receptors in the same membrane via lateral (cis) associations and regulation of cell-cell recognition by trans interaction with ganglioside binding proteins on apposing cells. Gangliosides also affect the aggregation of Aβ (Alzheimer's disease) and α-synuclein (Parkinson's Disease). As analytical, biochemical, and genetic tools advance, research on gangliosides promises to reveal mechanisms of molecular control related to nerve and glial cell differentiation, neuronal excitability, axon outgrowth after nervous system injury, and protein folding in neurodegenerative diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. EPR and optical absorption studies on Gd 3+ ions in ammonium hydrogen malonate single crystals

    NASA Astrophysics Data System (ADS)

    Kripal, Ram; Mishra, Indrajeet

    2010-01-01

    X-Band electron paramagnetic resonance (EPR) studies of Gd 3+ ions in ammonium hydrogen malonate single crystals have been done at room temperature. Detailed EPR analysis indicates the presence of four physically equivalent but magnetically inequivalent sites. The zero-field splitting parameters and g factor are determined. The Gd 3+ ion is in 8S state; its levels are split by the action of the crystalline electric field of monoclinic symmetry. The optical absorption spectra of Gd 3+ ions in single crystals of ammonium hydrogen malonate are also recorded at room temperature. The energy levels of the 4f 7 configuration are calculated and compared with those observed experimentally. The values of E1=5854±11, E2=31±0.36, E3=592±3.3 and ζ 4f=1595±25 cm -1 are found to give the best over-all agreement between experimentally observed and calculated levels.

  15. Effect of pressure on nanostructured Gd3Fe5O12

    NASA Astrophysics Data System (ADS)

    Rovani, P. R.; Ferreira, A. S.; Pereira, A. S.; de Lima, J. C.

    2017-07-01

    The effect of pressure on mechanically alloyed nanostructured Gd3Fe5O12 was investigated using in situ angle-dispersive X-ray diffraction measurements at room temperature. No structural phase transitions were observed, but an anomalous behavior in the volume vs. pressure curve, attributed to nonhydrostatic effects, was observed in the pressure range between 4.4 GPa and 9.1 GPa. The analysis of effect of pressure on the Wickoff 23c sites, occupied by Gd3+ ions, 16a and 24d sites, occupied by Fe3+ ions, and 96h sites, occupied by O2- ions, was performed. The value of the bulk modulus B0 for nanostructured Gd3Fe5O12 could not be determined due to nonhydrostatic effects associated with the silicone oil used as a pressure transmitting medium.

  16. Gd3+ vibronic side band spectroscopy. New optical probe of Ca2+ binding sites applied to biological macromolecules.

    PubMed Central

    Iben, I E; Stavola, M; Macgregor, R B; Zhang, X Y; Friedman, J M

    1991-01-01

    A new spectroscopic technique is presented for obtaining infraredlike spectra of the binding sites of Ca2+ and other metals in biological macromolecules. The technique, based on the Ca(2+)-like binding properties of Gd3+, utilizes vibronic side bands (VSB) that appear in Gd3+ fluorescence. In the fluorescence spectrum of Gd3+, the separation in photon frequency between a VSB and its electronic origin at approximately 32,150 cm-1 (approximately 311 nm) is a direct measure of the vibrational frequency of a ligand coordinated to Gd3+ ion. As a consequence, the VSB are uncomplicated by molecular vibrations distant from the Gd3+ binding site. The vibrational spectra resulting from the VSB of Gd3+ coordinated to a Ca2+ binding protein, a phospholipid, and DNA are presented. PMID:1907866

  17. Unique Ganglioside Recognition Strategies for Clostridial Neurotoxins

    SciTech Connect

    Benson, Marc A.; Fu, Zhuji; Kim, Jung-Ja P.; Baldwin, Michael R.

    2012-03-15

    Botulinum neurotoxins (BoNTs) and tetanus neurotoxin are the causative agents of the paralytic diseases botulism and tetanus, respectively. The potency of the clostridial neurotoxins (CNTs) relies primarily on their highly specific binding to nerve terminals and cleavage of SNARE proteins. Although individual CNTs utilize distinct proteins for entry, they share common ganglioside co-receptors. Here, we report the crystal structure of the BoNT/F receptor-binding domain in complex with the sugar moiety of ganglioside GD1a. GD1a binds in a shallow groove formed by the conserved peptide motif E ... H ... SXWY ... G, with additional stabilizing interactions provided by two arginine residues. Comparative analysis of BoNT/F with other CNTs revealed several differences in the interactions of each toxin with ganglioside. Notably, exchange of BoNT/F His-1241 with the corresponding lysine residue of BoNT/E resulted in increased affinity for GD1a and conferred the ability to bind ganglioside GM1a. Conversely, BoNT/E was not able to bind GM1a, demonstrating a discrete mechanism of ganglioside recognition. These findings provide a structural basis for ganglioside binding among the CNTs and show that individual toxins utilize unique ganglioside recognition strategies.

  18. Ceramide structure predicts tumor ganglioside immunosuppressive activity.

    PubMed Central

    Ladisch, S; Li, R; Olson, E

    1994-01-01

    Molecular determinants of biological activity of gangliosides are generally believed to be carbohydrate in nature. However, our studies of immunomodulation by highly purified naturally occurring tumor gangliosides provide another perspective: while the immunosuppressive activity of gangliosides requires the intact molecule (both carbohydrate and ceramide moieties), ceramide structure strikingly influences ganglioside immunosuppressive activity. Molecular species of human neuroblastoma GD2 ganglioside in which the ceramide contains a shorter fatty acyl chain (C16:0, C18:0) were 6- to 10-fold more active than those with a longer fatty acyl chain (C22:0/C24:1, C24:0). These findings were confirmed in studies of ceramide species of human leukemia sialosylparagloboside and murine lymphoma GalNAcGM1b. Gangliosides that contain shorter-chain fatty acids (and are most immunosuppressive) are known to be preferentially shed by tumor cells. Therefore, the results suggest that the tumor cell is optimized to protect itself from host immune destruction by selective shedding of highly active ceramide species of gangliosides. Images PMID:8127917

  19. Ganglioside Regulation of AMPA Receptor Trafficking

    PubMed Central

    Prendergast, Jillian; Umanah, George K.E.; Yoo, Seung-Wan; Lagerlöf, Olof; Motari, Mary G.; Cole, Robert N.; Huganir, Richard L.; Dawson, Ted M.; Dawson, Valina L.

    2014-01-01

    Gangliosides are major cell-surface determinants on all vertebrate neurons. Human congenital disorders of ganglioside biosynthesis invariably result in intellectual disability and are often associated with intractable seizures. To probe the mechanisms of ganglioside functions, affinity-captured ganglioside-binding proteins from rat cerebellar granule neurons were identified by quantitative proteomic mass spectrometry. Of the six proteins that bound selectively to the major brain ganglioside GT1b (GT1b:GM1 > 4; p < 10−4), three regulate neurotransmitter receptor trafficking: Thorase (ATPase family AAA domain-containing protein 1), soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (γ-SNAP), and the transmembrane protein Nicalin. Thorase facilitates endocytosis of GluR2 subunit-containing AMPA-type glutamate receptors (AMPARs) in an ATPase-dependent manner; its deletion in mice results in learning and memory deficits (J. Zhang et al., 2011b). GluR2-containing AMPARs did not bind GT1b, but bound specifically to another ganglioside, GM1. Addition of noncleavable ATP (ATPγS) significantly disrupted ganglioside binding, whereas it enhanced AMPAR association with Thorase, NSF, and Nicalin. Mutant mice lacking GT1b expressed markedly higher brain Thorase, whereas Thorase-null mice expressed higher GT1b. Treatment of cultured hippocampal neurons with sialidase, which cleaves GT1b (and other sialoglycans), resulted in a significant reduction in the size of surface GluR2 puncta. These data support a model in which GM1-bound GluR2-containing AMPARs are functionally segregated from GT1b-bound AMPAR-trafficking complexes. Release of ganglioside binding may enhance GluR2-containing AMPAR association with its trafficking complexes, increasing endocytosis. Disrupting ganglioside biosynthesis may result in reduced synaptic expression of GluR2-contianing AMPARs resulting in intellectual deficits and seizure susceptibility in mice and humans. PMID:25253868

  20. Ganglioside regulation of AMPA receptor trafficking.

    PubMed

    Prendergast, Jillian; Umanah, George K E; Yoo, Seung-Wan; Lagerlöf, Olof; Motari, Mary G; Cole, Robert N; Huganir, Richard L; Dawson, Ted M; Dawson, Valina L; Schnaar, Ronald L

    2014-09-24

    Gangliosides are major cell-surface determinants on all vertebrate neurons. Human congenital disorders of ganglioside biosynthesis invariably result in intellectual disability and are often associated with intractable seizures. To probe the mechanisms of ganglioside functions, affinity-captured ganglioside-binding proteins from rat cerebellar granule neurons were identified by quantitative proteomic mass spectrometry. Of the six proteins that bound selectively to the major brain ganglioside GT1b (GT1b:GM1 > 4; p < 10(-4)), three regulate neurotransmitter receptor trafficking: Thorase (ATPase family AAA domain-containing protein 1), soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (γ-SNAP), and the transmembrane protein Nicalin. Thorase facilitates endocytosis of GluR2 subunit-containing AMPA-type glutamate receptors (AMPARs) in an ATPase-dependent manner; its deletion in mice results in learning and memory deficits (J. Zhang et al., 2011b). GluR2-containing AMPARs did not bind GT1b, but bound specifically to another ganglioside, GM1. Addition of noncleavable ATP (ATPγS) significantly disrupted ganglioside binding, whereas it enhanced AMPAR association with Thorase, NSF, and Nicalin. Mutant mice lacking GT1b expressed markedly higher brain Thorase, whereas Thorase-null mice expressed higher GT1b. Treatment of cultured hippocampal neurons with sialidase, which cleaves GT1b (and other sialoglycans), resulted in a significant reduction in the size of surface GluR2 puncta. These data support a model in which GM1-bound GluR2-containing AMPARs are functionally segregated from GT1b-bound AMPAR-trafficking complexes. Release of ganglioside binding may enhance GluR2-containing AMPAR association with its trafficking complexes, increasing endocytosis. Disrupting ganglioside biosynthesis may result in reduced synaptic expression of GluR2-contianing AMPARs resulting in intellectual deficits and seizure susceptibility in mice and humans.

  1. Influence of dietary gangliosides on neonatal brain development.

    PubMed

    McJarrow, Paul; Schnell, Nicholas; Jumpsen, Jacqueline; Clandinin, Tom

    2009-08-01

    Gangliosides are sialic acid-containing glycosphingolipids. Gangliosides are found in human milk; understanding of the potential role of gangliosides in infant development is emerging, with suggested roles in the brain and gut. Ganglioside accretion in the developing brain is highest in utero and in early neonatal life, during the periods of dendritic branching and new synapse formation. Further, brain contains the highest relative ganglioside content in the body, particularly in neuronal cell membranes concentrated in the area of the synaptic membrane. Gangliosides are known to play a role in neuronal growth, migration and maturation, neuritogenesis, synaptogenesis, and myelination. In addition to their roles in development and structure of the brain, gangliosides also play a functional role in nerve cell communication. It is less well known whether dietary gangliosides can influence the development of cognitive function. This review summarizes current knowledge on the role gangliosides play in brain development.

  2. Inter-atomic bonding and dielectric polarization in Gd3+ incorporated Co-Zn ferrite nanoparticles

    NASA Astrophysics Data System (ADS)

    Pawar, R. A.; Desai, S. S.; Patange, S. M.; Jadhav, S. S.; Jadhav, K. M.

    2017-04-01

    A series of ferrite with a chemical composition Co0.7Zn0.3GdxFe2-xO4 (where x=0.0 to x=0.1) were prepared by sol-gel auto-combustion method. X-ray diffraction pattern were used to determine the crystal structure and phase formation of the prepared samples. Scanning electron microscopy is used to study the surface morphology of the prepared samples. Elastic properties were determined from the infrared spectroscopy. Debye temperature, wave velocities, elastic constants found to increase with the increase in Gd3+ substitution. Dielectric properties such as dielectric constant and dielectric loss were studied as a function of Gd3+ substitution and frequency. Dielectric constant decreased with the increase in frequency and Gd3+ substitution. Behavior of dielectric properties was explained on the basis of Maxwell-Wagner interfacial polarization which in accordance with Koops phenomenological theory. Real and imaginary part of impedance was studied as a function of resistance and Gd3+ substitution. The behavior of impedance is systematically discussed on the basis of resistance-capacitance circuit.

  3. Phase formation and UV luminescence of Gd3+ doped perovskite-type YScO3

    NASA Astrophysics Data System (ADS)

    Shimizu, Yuhei; Ueda, Kazushige

    2016-10-01

    Synthesis of pure and Gd3+doped perovskite-type YScO3 was attempted by a polymerized complex (PC) method and solid state reaction (SSR) method. Crystalline phases and UV luminescence of samples were examined with varying heating temperatures. The perovskite-type single phase was not simply formed in the SSR method, as reported in some literatures, and two cubic C-type phases of starting oxide materials remained forming slightly mixed solid solutions. UV luminescence of Gd3+ doped samples increased with an increase in heating temperatures and volume of the perovskite-type phase. In contrast, a non-crystalline precursor was crystallized to a single C-type phase at 800 °C in the PC method forming a completely mixed solid solution. Then, the phase of perovskite-type YScO3 formed at 1200 °C and its single phase was obtained at 1400 °C. It was revealed that high homogeneousness of cations was essential to generate the single perovskite-phase of YScO3. Because Gd3+ ions were also dissolved into the single C-type phase in Gd3+ doped samples, intense UV luminescence was observed above 800 °C in both C-type phase and perovskite-type phase.

  4. Nanostructured Gd3+-TiO2 surfaces for self-cleaning application

    NASA Astrophysics Data System (ADS)

    Saif, M.; El-Molla, S. A.; Aboul-Fotouh, S. M. K.; Ibrahim, M. M.; Ismail, L. F. M.; Dahn, Douglas C.

    2014-06-01

    Preparation of self-cleaning surfaces based on lanthanide modified titanium dioxide nanoparticles has rarely been reported. In the present work, gadolinium doped titanium dioxide thin films (x mol Gd3+-TiO2 where x = 0.000, 0.005, 0.008, 0.010, 0.020 and 0.030 mol) were synthesized by sol-gel method and deposited using doctor-blade method. These films were characterized by studying their structural, optical and electrical properties. Doping with gadolinium decreases the band gap energy and increase conductivity of thin films. The photo self-cleaning activity in term of quantitative determination of the active oxidative species (rad OH) produced on the thin film surfaces was evaluated using fluorescent probe method. The results show that, the highly active thin film is the 0.020 Gd3+-TiO2. The structural, morphology, optical, electrical and photoactivity properties of Gd3+-TiO2 thin films make it promising surfaces for self-cleaning application. Mineralization of commercial textile dye (Remazol Red RB-133, RR) and durability using 0.020Gd3+-TiO2 film surface was studied.

  5. Anti-ganglioside antibodies in patients with systemic lupus erythematosus and neurological manifestations.

    PubMed

    Labrador-Horrillo, M; Martinez-Valle, F; Gallardo, E; Rojas-Garcia, R; Ordi-Ros, J; Vilardell, M

    2012-05-01

    Anti-ganglioside antibodies (AGA) have been associated with several peripheral neuropathies, such as Miller-Fisher syndrome, Guillain-Barré syndrome and multifocal motor neuropathy. They have also been studied in patients with systemic lupus erythematosus (SLE), focusing on neuropsychiatric manifestations and peripheral neuropathy, but the results are contradictory. To study the presence of AGA in a large cohort of patients with SLE and neuropsychiatric manifestations. Serum from 65 consecutive patients with SLE and neuropsychiatric manifestations, collected from 1985 to 2009, was tested for the presence of AGA antibodies (GM1, GM2, GM3, asialo-GM1 GD1a, GD1b, GD3, GT1b, GQ1b) using a standard enzyme-linked immunosorbent assay ELISA test (INCAT 1999) and thin layer chromatography (TLC). Positive results for asialo-GM1 (IgM) were found in 10 patients, 6 were positive for asialo-GM1 (IgM and IgG), and 4 were positive for other AGA such as GM1, GM2, GM3, GD1b, GT1b, GD3, (mainly IgM). Clinical and statistical studies showed no correlation between AGA and neuropsychiatric manifestations of SLE. Although some patients showed reactivity to AGA, these antibodies are not a useful marker of neuropsychiatric manifestations in SLE patients.

  6. Recognition characteristics of monoclonal antibodies that are cross-reactive with gangliosides and lipooligosaccharide from Campylobacter jejuni strains associated with Guillain-Barré and Fisher syndromes.

    PubMed

    Houliston, R Scott; Yuki, Nobuhiro; Hirama, Tomoko; Khieu, Nam H; Brisson, Jean-Robert; Gilbert, Michel; Jarrell, Harold C

    2007-01-09

    The enteropathogen Campylobacter jejuni has the ability to synthesize glycan structures that are similar to mammalian gangliosides within the core component of its lipooligosaccharide (LOS). Exposure to ganglioside mimics in some individuals results in the production of autoantibodies that deleteriously attack nerve surface gangliosides, precipitating the onset of Guillain-Barré and Fisher syndromes (GBS and FS). We have characterized the interaction of four monoclonal antibodies (mAbs), established by sensitization of mice with LOS isolated from GBS- and FS-associated C. jejuni strains, with chemoenzymatically synthesized gangliooligosaccharides. Surface plasmon resonance (SPR) measurements demonstrate that three of the mAbs interact specifically with derivatives corresponding to their targeted gangliosides, with dissociation constants ranging from 10 to 20 microM. Antibody binding to the gangliooligosaccharides was probed by saturation transfer difference (STD) NMR spectroscopy. STD signals, resulting from antibody/oligosaccharide interaction, were observed for each of the four mAbs. In two cases, differential saturation transfer rates to oligosaccharide resonances enabled detailed epitope mapping. The binding of GD1a-S-Phe with GB1 is characterized by close association of the immunoglobulin with sites that are distributed over several residues of the oligosaccharide. This contrasts sharply with the profile observed for the binding of both GD3-S-Phe and GT1a-S-Phe with FS1. The close antigenic contacts in these ganglioside derivatives are confined to the N-acetylmannosaminyl portion of the terminal N-acetylneuraminic acid (NeuAc) residue of the disialosyl moiety. Our characterization of FS1 provides insight, at an atomic level, into how a single antigenic determinant presented by the LOS of C. jejuni can give rise to antibodies with binding promiscuity to [alphaNeuAc-(2-8)-alphaNeuAc]-bound epitopes and demonstrates why sera from FS patients have antibodies that

  7. Motor-dominant polyneuropathy due to IgM monoclonal antibody against disialosyl gangliosides in a patient with mantle cell lymphoma.

    PubMed

    Mori, Akio; Ueno, Yuji; Kuroki, Takuma; Hoshino, Yasunobu; Shimura, Hideki; Sekiguchi, Yasunobu; Noguchi, Masaaki; Hamada, Yukihiro; Kusunoki, Susumu; Hattori, Nobutaka; Urabe, Takao

    2014-02-15

    A rapidly progressive motor-dominant neuropathy associated with IgM monoclonal antibody against gangliosides with disialosyl residues, GD3, GD1b, GT1b, and GQ1b, in a 60-year-old Japanese man with mantle cell lymphoma is reported. Plasma exchange and chemotherapy for mantle cell lymphoma were performed for the neuropathy and mantle cell lymphoma. After therapy, the motor neuropathy dramatically improved concurrently with substantial reduction of the antibody activities especially in reaction to GD1b. This is the first case report of neuropathy with anti-disialosyl IgM antibodies associated with mantle cell lymphoma, and plasma exchange and chemotherapy were effective.

  8. Elevation of GM2 ganglioside during ethanol-induced apoptotic neurodegeneration in the developing mouse brain.

    PubMed

    Saito, Mitsuo; Chakraborty, Goutam; Shah, Relish; Mao, Rui-Fen; Kumar, Asok; Yang, Dun-Sheng; Dobrenis, Kostantin; Saito, Mariko

    2012-05-01

    GM2 ganglioside in the brain increased during ethanol-induced acute apoptotic neurodegeneration in 7-day-old mice. A small but a significant increase observed 2 h after ethanol exposure was followed by a marked increase around 24 h. Subcellular fractionation of the brain 24 h after ethanol treatment indicated that GM2 increased in synaptic and non-synaptic mitochondrial fractions as well as in a lysosome-enriched fraction characteristic to the ethanol-exposed brain. Immunohistochemical staining of GM2 in the ethanol-treated brain showed strong punctate staining mainly in activated microglia, in which it partially overlapped with staining for LAMP1, a late endosomal/lysosomal marker. Also, there was weaker neuronal staining, which partially co-localized with complex IV, a mitochondrial marker, and was augmented in cleaved caspase 3-positive neurons. In contrast, the control brain showed only faint and diffuse GM2 staining in neurons. Incubation of isolated brain mitochondria with GM2 in vitro induced cytochrome c release in a manner similar to that of GD3 ganglioside. Because ethanol is known to trigger mitochondria-mediated apoptosis with cytochrome c release and caspase 3 activation in the 7-day-old mouse brain, the GM2 elevation in mitochondria may be relevant to neuroapoptosis. Subsequently, activated microglia accumulated GM2, indicating a close relationship between GM2 and ethanol-induced neurodegeneration.

  9. Influence of Rare Earth (Gd3+) on Structural, Gigahertz Dielectric and Magnetic Studies of Cobalt ferrite

    NASA Astrophysics Data System (ADS)

    Pervaiz, Erum; Gul, I. H.

    2013-06-01

    A series of Gd3+ doped nanocrystalline Co-ferrites CoGdxFe2-xO4 (x = 0.0 to 0.1) has been prepared by sol-gel auto combustion technique. Structural and morphology studies were performed using X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM). Indexed XRD patterns confirm the formation of pure cubic spinel phase. Average crystallite sizes ranges from 16 nm to 25 nm ±2, were calculated from Sherrer's formula and Williamson Hall plots. Crystal strain increases with increase in doping amount of trivalent Gd ion. Lattice constant (a) and crystallite size D (311) increases with increase in Gd3+ concentration due to large ionic radii (0.94nm) of Gd3+ replacing Fe3+ (0.64nm). SEM images show the spherical morphology and uniform size distribution. Room temperature DC electrical resistivity decreases (~106) for x=0.025 then increases up to x=0.1 ~ (4.5×107). Dielectric properties have been studied using RF Impedance/material analyzer in the frequency range of 1 MHz to 1GHz. All the studied samples show a semi-conducting behavior as Permittivity and tangent loss (tanδ) decreases with the substitution of Gd3+ in parent crystal structure and have values of 4.92 and 0.016 at 1 GHz respectively. Complex impedance and Complex electric modulus plots were further studied for complete contribution of grains and grain boundary resistances to conduction and resonance frequencies respectively. Magnetic studies by Vibrating Sample Magnetometer (VSM) shows that magnetization (Ms) decreases with increase in Gd3+ concentration from 63 emu/gm to 27.26 emu/gm. Coercivity (Hc) first decreases for x=0.025, after which it increases to 2308 Oe for x=0.1.

  10. Absorption Spectra and Energy Levels of Gd(3+), Nd(3+), and Cr(3+) in the Garnet Gd3Sc2Ga3O12.

    DTIC Science & Technology

    1988-03-01

    The doping of GSGG with neodymium and chromium is better controlled as compared with Y3AI50 2 ( YAG ), The dopant distribution is governed by the same...liquid helium temperature. z . . . . .. . . . . . . 3400 3;03 3 i00 - aF~i WAVE LIENG Tm A n18 e!4 Figure 8. Absorption spectrum ofL[6Pl7/21(A CBfl...Splitting Calculations: Nd 3+, Gd3 The material GSGG is a mixed garnet with the same crystal structure as Y3A150 12 ( YAG ) 121,221. The cubic space group is

  11. Physiopathological function of hematoside (GM3 ganglioside)

    PubMed Central

    INOKUCHI, Jin-ichi

    2011-01-01

    Since I was involved in the molecular cloning of GM3 synthase (SAT-I), which is the primary enzyme for the biosynthesis of gangliosides in 1998, my research group has been concentrating on our efforts to explore the physiological and pathological implications of gangliosides especially for GM3. During the course of study, we demonstrated the molecular pathogenesis of type 2 diabetes and insulin resistance focusing on the interaction between insulin receptor and gangliosides in membrane microdomains and propose a new concept: Life style-related diseases, such as type 2 diabetes, are a membrane microdomain disorder caused by aberrant expression of gangliosides. We also encountered an another interesting aspect indicating the indispensable role of gangliosides in auditory system. After careful behavioral examinations of SAT-I knockout mice, their hearing ability was seriously impaired with selective degeneration of the stereocilia of hair cells in the organ of Corti. This is the first observation demonstrating a direct link between gangliosides and hearing functions. PMID:21558756

  12. Circulating gangliosides of breast-cancer patients.

    PubMed

    Wiesner, D A; Sweeley, C C

    1995-01-27

    Gangliosides were isolated from the sera of recently diagnosed breast-cancer patients and from individuals who were apparently free of disease. Quantificative and qualitative analyses were carried out by 2-dimensional high-performance thin-layer chromatography and gas chromatography. The locations of isolated gangliosides on thin-layer chromatograms were determined by visualization with resorcinol, and each spot was quantified by digital image densitometry. The ganglioside profiles of cancer patients were compared to those of the control group, revealing a significant increase in total lipid-bound sialic acid and a specific increase in polysialogangliosides in the patients with breast cancer. Furthermore, an increase was noted in the ratio of gangliosides of the b-series biosynthetic pathway over those of the a-series in the cancer sera, as compared to the controls. Gas chromatographic analysis of the peracetylated methanolysis mixtures derived from the total ganglioside fraction of cancer patients supported the HPTLC data, with an increase in total sialic acid, galactose, and sphingosine residues. No unusual gangliosides were found in the mixture from breast-cancer patients.

  13. Monitoring Diabetic Nephropathy by Circulating Gangliosides.

    PubMed

    Ene, Corina Daniela; Penescu, Mircea; Anghel, Amalia; Neagu, Monica; Budu, Vlad; Nicolae, Ilinca

    2016-01-01

    Gangliosides are multifunctional molecules, abundantly expressed in renal cell membrane but also in sera of patients with renal disease. The aim of this study was to quantify the serum levels of sialic acid-ganglioside in patients diagnosed with diabetes for an eventual biomarker stratification of patients with renal complications. We included 35 diabetic patients without metabolic complications, 35 patients with diabetic nephropathy, 35 non-diabetic individuals. We found that sialic acid ganglioside serum level was significantly increased in patients with diabetic nephropathy compared to the level obtained in patients with uncomplicated diabetes and to non-diabetic controls. A statistically significant positive correlation was obtained between serum levels of sialic acid gangliosides, HbA1c, and serum creatinine in patients with diabetes without complications. Moreover positive correlation was found between sialic acid ganglioside and blood glucose, HbA1c, urea, creatinine, microalbuminuria in patients with diabetic nephropathy. We can conclude that serum sialic acid-gangliosides are statistically increased in diabetic nephropathy positively correlated with microalbuminuria.

  14. Influence of gangliosides on the IL-2- and IL-4-dependent cell proliferation.

    PubMed

    Molotkovskaya, Irina M; Kholodenko, Roman V; Molotkovsky, Julian G

    2002-08-01

    Ganglioside-induced apoptosis in the cells of IL-2-dependent cytotoxic murine cell line CTLL-2 was shown to be caspase dependent: GM1-, GM2-, and GD3-induced suppression of cell proliferation was cancelled by a general caspase inhibitor Z-VAD-FMK. Ganglioside-induced apoptosis pathways are different for different individual glycolipids; the differences exist both at the initiation and effector stages of the caspase cascade. Only for GM1-induced process, molecular mechanisms of signal transduction coincide with the ones for CD95 and TNFalpha: the participation of both the main initiation caspases 8, 1, and 4, and caspases 3 and 9 as well, has been shown. Caspase 3 participates in the pathway induced by GM3, GD1a, GD1b, and GT1b, but not by GM2. As morphological features show, tumor-associated ganglioside GM2 is also a stimulus of programmed cell death (PCD) for CTLL-2 cell line: addition of GM2 into cell culture has resulted in appearance of annexin V-positive cells and in accumulation of DNA breaks (shown by the TUNEL direct dyeing of the open ends). But a caspase 3 inhibitor Z-DEVD-FMK did not restore the cell proliferation suppressed by GM2, and addition of a fluorescent substrate of caspase 3 Ac-DEVD-AFC did not result in the fluorescence development. So caspase 3 does not participate in downstream pathways of GM2-induced cell apoptosis, and a PCD-effector system other than the apoptosome-mediated one is involved here.

  15. Ganglioside synthase knockout in oncogene-transformed fibroblasts depletes gangliosides and impairs tumor growth.

    PubMed

    Liu, Y; Yan, S; Wondimu, A; Bob, D; Weiss, M; Sliwinski, K; Villar, J; Notario, V; Sutherland, M; Colberg-Poley, A M; Ladisch, S

    2010-06-03

    Biologically active membrane gangliosides, expressed and released by many human tumors, are hypothesized to significantly impact tumor progression. Lack of a model of complete and specific tumor ganglioside depletion in vivo, however, has hampered elucidation of their role. Here, we report the creation of a novel, stable, genetically induced tumor cell system resulting in specific and complete blockade of ganglioside synthesis. Wild-type (WT) and GM3 synthase/GM2 synthase double knockout (DKO) murine embryonic fibroblasts were transformed using amphotropic retrovirus-transduced oncogenes (pBABE-c-Myc(T58A)+H-RasG12V). The transformed cells, WT(t) and DKO(t) respectively, evidenced comparable integrated copy numbers and oncogene expression. Ganglioside synthesis was completely blocked in the DKO(t) cells, importantly without triggering an alternate pathway of ganglioside synthesis. Ganglioside depletion (to <0.5 nmol/10(7) cells from 9 to 11 nmol/10(7) WT(t) or untransfected normal fibroblasts) did not adversely affect cell proliferation kinetics but did reduce cell migration on fibronectin-coated wells, consistent with our previous observations in ganglioside-depleted normal human fibroblasts. Strikingly, despite similar oncogene expression and growth kinetics, DKO(t) cells evidenced significantly impaired tumor growth in syngeneic immunocompetent mice, underscoring the pivotal role of tumor cell gangliosides and providing an ideal system for probing their mechanisms of action in vivo.

  16. Ganglioside synthase knockout in oncogene-transformed fibroblasts depletes gangliosides and impairs tumor growth

    PubMed Central

    Liu, Yihui; Yan, Su; Wondimu, Assefa; Bob, Daniel; Weiss, Michael; Sliwinski, Konrad; Villar, Joaquín; Notario, Vicente; Sutherland, Margaret; Colberg-Poley, Anamaris M.; Ladisch, Stephan

    2010-01-01

    Biologically active membrane gangliosides, expressed and released by many human tumors, are hypothesized to significantly impact tumor progression. Lack of a model of complete and specific tumor ganglioside depletion in vivo, however, has hampered elucidation of their role. Here we report the creation of a novel, stable, genetically induced tumor cell system resulting in specific and complete blockade of ganglioside synthesis. Wild type (WT) and GM3 synthase/GM2 synthase double knockout (DKO) murine embryonic fibroblasts were transformed using amphotropic retrovirus-transduced oncogenes (pBABE-c-MycT58A+H-RasG12V). The transformed cells, WTt and DKOt respectively, evidenced comparable integrated copy numbers and oncogene expression. Ganglioside synthesis was completely blocked in the DKOt cells, importantly without triggering an alternate pathway of ganglioside synthesis. Ganglioside depletion (to <0.5 nmol/107 cells from 9-11 nmol/107 WTt or untransfected normal fibroblasts) did not adversely affect cell proliferation kinetics but did reduce cell migration on fibronectin-coated wells, consistent with our previous observations in ganglioside-depleted normal human fibroblasts. Strikingly, despite similar oncogene expression and growth kinetics, DKOt cells evidenced significantly impaired tumor growth in syngeneic immunocompetent mice, underscoring the pivotal role of tumor cell gangliosides and providing an ideal system for probing their mechanisms of action in vivo. PMID:20305696

  17. The photoluminescence, drug delivery and imaging properties of multifunctional Eu3+/Gd3+ dual-doped hydroxyapatite nanorods.

    PubMed

    Chen, Feng; Huang, Peng; Zhu, Ying-Jie; Wu, Jin; Zhang, Chun-Lei; Cui, Da-Xiang

    2011-12-01

    The design and synthesis of multifunctional systems with high biocompatibility are very significant for the future of clinical applications. Herein, we report a microwave-assisted rapid synthesis of multifunctional Eu(3+)/Gd(3+) dual-doped hydroxyapatite (HAp) nanorods, and the photoluminescence (PL), drug delivery and in vivo imaging of as-prepared Eu(3+)/Gd(3+) doped HAp nanorods. The photoluminescent and magnetic multifunctions of HAp nanorods are realized by the dual-doping with Eu(3+) and Gd(3+). The PL intensity of doped HAp nanorods can be adjusted by varying Eu(3+) and Gd(3+) concentrations. The magnetization of doped HAp nanorods increases with the concentration of doped Gd(3+). The as-prepared Eu(3+)/Gd(3+)-doped HAp nanorods exhibit inappreciable toxicity to the cells in vitro. More importantly, the Eu(3+)/Gd(3+)-doped HAp nanorods show a high drug adsorption capacity and sustained drug release using ibuprofen as a model drug, and the drug release is governed by a diffusion process. Furthermore, the noninvasive visualization of nude mice with subcutaneous injection indicates that the Eu(3+)/Gd(3+)-doped HAp nanorods with the photoluminescent function are suitable for in vivo imaging. In vitro and in vivo imaging tests indicate that Eu(3+)/Gd(3+)-doped HAp nanorods have a potential in applications such as a multiple-model imaging agent for magnetic resonance (MR) imaging, photoluminescence imaging and computed tomography (CT) imaging. The Eu(3+)/Gd(3+) dual-doped HAp nanorods are promising for applications in the biomedical fields such as multifunctional drug delivery systems with imaging guidance.

  18. Gangliosides During Tumor Progression in Patients With Prostate Cancer

    DTIC Science & Technology

    2002-07-01

    Objectives of the project are: (1) to identify the gangliosides of Prostate cancer (CaP) cells that are immunogenic so that they can be used as...targets to develop immunotherapy for prostate cancer; (2) to determine the total and specific Cap- gangliosides released into the blood and (3) to assess...the nature of immunosuppression induced by CaP gangliosides . The major findings of the first year are as follows: Ganglioside GM1 is the major cell

  19. STUDIES ON GANGLIOSIDES FROM HUMAN AND CALF BRAIN.

    DTIC Science & Technology

    Attempts to characterize the individual gangliosides by component molar ratios have indicated a requirement for reliable glucose and galactose assays...milligram amounts of ganglioside . When this GLC assay was used to characterize a preparation which appeared to be an unreported ganglioside , the data...of the most recent literature that no single TLC solvent system was adequate to distinguish the numerous ganglioside species which were reported

  20. Persistent luminescence in powdered and ceramic polycrystalline Gd3Al2Ga3O12:Ce

    NASA Astrophysics Data System (ADS)

    Dosovitskiy, G.; Fedorov, A.; Mechinsky, V.; Borisevich, A.; Dosovitskiy, A.; Tret’jak, E.; Korjik, M.

    2017-02-01

    This paper studies powders of Gd3Ga3Al2O12:Ce, a promising scintillator composition, as a possible object for express pre-characterization of scintillation kinetics and level of persistent luminescence. Garnet phase powders with uniform microstructure, consisting of 1-2 μm grains, were obtained by co-precipitation approach. It was shown, that both scintillation decay time and presence of persistent luminescence are influenced by both powder thermal treatment temperature and strong Ga deficit.

  1. Enhanced MRI relaxivity of aquated Gd3+ ions by carboxyphenylated water-dispersed graphene nanoribbons.

    PubMed

    Gizzatov, Ayrat; Keshishian, Vazrik; Guven, Adem; Dimiev, Ayrat M; Qu, Feifei; Muthupillai, Raja; Decuzzi, Paolo; Bryant, Robert G; Tour, James M; Wilson, Lon J

    2014-03-21

    The present study demonstrates that highly water-dispersed graphene nanoribbons dispersed by carboxyphenylated substituents and conjugated to aquated Gd(3+) ions can serve as a high-performance contrast agent (CA) for applications in T1- and T2-weighted magnetic resonance imaging (MRI) with relaxivity (r1,2) values outperforming currently-available clinical CAs by up to 16 times for r1 and 21 times for r2.

  2. A new approach to the modification of cell membrane glycosphingolipids: Ganglioside composition of JTC-12 P3 cells altered by feeding with galactose as a sole carbohydrate source in protein- and lipid-free synthetic medium

    SciTech Connect

    Kawaguchi, Tatsuya Kumamoto Univ. Medical School ); Takaoka, Toshiko; Yoshida, Eiko ); Iwamori, Masao; Nagai, Yoshitaka Niigata Univ. ); Takatsuki, Kiyoshi )

    1988-12-01

    A significant difference in the glycosphingolipid composition of JTC-12 P3 cells established from monkey kidney tissue was observed when cells cultured in a protein- and lipid-free synthetic medium containing glucose (DM-160) as a sole carbohydrate source were transferred and cultured in the same medium containing galactose and pyruvic acid (DM-170) in place of glucose. In particular, the amounts of gangliosides GM3, GM2, and GD3 in the cells cultured in DM-170 were 5.3-, 17.8-, and more than 8-fold those in the cells cultured in DM-160, respectively, indicating that anabolism of gangliosides is greatly enhanced in cells cultured in the presence of galactose and pyruvic acid, as compared with cells cultured in the presence of glucose. In fact, after cultivation of cells in the medium with N-acetyl-D-({sup 14}C)mannosamine for 96 h, the radioactivity incorporated into the gangliosides of the cells in DM-170 was 10-fold that of the cells in DM-160. Among the gangliosides of the cells in DM-170, highly sialylated molecules such as GD3, GD1a, GD1b, and GT1b were preferentially labeled, indicating that the sialytransferases responsible for the synthesis of gangliosides are significantly more activated in cells cultured in DM-170 than in DM-160. These observations reveal that the glycosphingolipid composition of the plasma membrane can be modified epigenetically under well-defined conditions and provide important clues for clarifying the roles of glycosphingolipids associated with particular cell functions.

  3. An ab initio investigation on the endohedral metallofullerene Gd3N-C80

    NASA Astrophysics Data System (ADS)

    Qian, M. C.; Khanna, S. N.

    2007-05-01

    First-principles electronic structure studies on the ground state geometry and electronic and magnetic properties of bare and hydrogen coated metallofullerene Gd3N-C80 have been carried out within a density functional formalism. The correlation effects are incorporated either through a generalized gradient corrected functional or through an on-site Coulomb interaction (LDA+U). It is shown that the bare Gd3N-C80 possess a ferromagnetic ground state with a large spin moment of 21μB that is highly stable against spin fluctuations. The simulated Raman spectrum shows that the low-energy peaks are contributed by the floppy movement of N atom. As to the effect of addition of hydrogens, it is shown that the most favorable site for the hydrogen adsorption is an on-top site where the H atom is located above a five-member carbon ring with a binding energy of 1.92eV, while the least stable site corresponds to an on-top absorption above a six-member ring. A study of the energetics upon multiple adsorption of H shows that the binding energy of the H to metallofullerene drops after 11 H atoms. This shows that it should be possible to attach multiple ligands offering the potential that the Gd3N-C80 can be functionalized with ligands or assembled in cluster assemblies.

  4. Structural and dielectric behavior of Cr3+ and Gd3+ substituted Ni-Zn nano ferrites

    NASA Astrophysics Data System (ADS)

    Anupama M., K.; Jagadeesha Angadi, V.; Matteppanavar, Shidaling; Pattar, Vinayak; Rudraswamy, B.

    2016-05-01

    A series of Gd3+ doped nano crystalline Ni0.6Zn0.4Cr0.5GdxFe1.5-xO4 (where x=0. 00, 0.02, 0.04, 0.06) were prepared by solution combustion method using oxalyl dehydrazide (ODH) as a fuel. The Structural and dielectric behavior of as synthesized material was characterized through X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR). XRD pattern reveals that the formation of single phase with cubic spinel structure. The average crystallite size and lattice parameter were found to increase with increasing Gd3+ concentration. The FTIR spectra shows two strong absorption bands at 387 cm-1 and 564 cm-1 both represents tetrahedral and octahedral stretching bonds respectively. The dielectric properties were carried out as a function of frequency and composition with the frequency range 40Hz to 10MHz. All the samples show the collective contribution of n-type and p-type carriers. The permittivity were found to decrease with increasing of Gd3+ concentration this is due to hopping off electrons and charge transport which is typical characteristic of polar dielectrics. Complex impedance was studied to know the contribution of grains and grain boundary resistance has explained according to the Maxwell Wagener type two layer model.

  5. Enhanced photoluminescence in CaMoO4:Eu3+ by Gd3+ co-doping.

    PubMed

    Singh, B P; Parchur, A K; Ningthoujam, R S; Ansari, A A; Singh, P; Rai, S B

    2014-03-28

    We have studied the luminescence property of CaMoO4:Eu(3+). The emission peaks at 590 ((5)D0→(7)F1) and 613 nm ((5)D0→(7)F2) for Eu(3+) are observed after excitation at 266 nm (i.e. Mo-O charge transfer band). The peak intensity of the latter dominates over the former indicating an asymmetric environment of Eu(3+) in EuO8 polyhedron or parity mixing. Luminescence intensity increases significantly with co-doping of Gd(3+). This is ascribed to energy transfer from Mo-O/Gd(3+) to Eu(3+). Luminescence intensity increases with annealing up to 900 °C due to the extent of decrease of non-radiative rates. Very high asymmetric values (A21) of 12-16 are found indicating a red emitter. As-prepared samples are dispersible in polar solvents like water, ethanol, methanol, dimethyl sulfoxide (DMSO) and ethylene glycol (EG); and among them, optimum luminescence is found in methanol. Polymer film shows red emission. The quantum yields of as-prepared 2 and 10 at% Gd(3+) co-doped CaMoO4:Eu(3+) under 277 nm (UV excitation) are 21 and 80%, respectively.

  6. Impact of Gd3+ doping and glassing solvent deuteration on 13C DNP at 5 Tesla

    NASA Astrophysics Data System (ADS)

    Kiswandhi, Andhika; Lama, Bimala; Niedbalski, Peter; Goderya, Mudrekh; Long, Joanna; Lumata, Lloyd

    Dynamic nuclear polarization (DNP) is a technique which can be used to amplify signals in nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) by several thousand-fold. The most commonly available DNP system typically operates at the W-band field or 3.35 T, at which it has been shown that 13C NMR signal can be enhanced by deuteration and Gd3+ doping. In this work, we have investigated the applicability of these procedures at 5 T. Our results indicate that the deuteration of the glassing matrix still yields an enhancement of 13C DNP when 4-oxo-TEMPO free radical is used. The effect is attributed to the lower heat load of the deuterons compared to protons. An addition of a trace amount of Gd3+ gives a modest enhancement of the signal when trityl OX063 is used, albeit with a less pronounced relative enhancement compared to the results obtained at 3.35 T. The results suggest that the enhancement obtained via Gd3+ doping may become saturated at higher field. These results will be discussed using a thermodynamic model of DNP. This work is supported by US Dept of Defense Award No. W81XWH-14-1-0048 and Robert A. Welch Foundation Grant No. AT-1877.

  7. Macrocyclic Gd(3+) complexes with pendant crown ethers designed for binding zwitterionic neurotransmitters.

    PubMed

    Oukhatar, Fatima; Meudal, Hervé; Landon, Céline; Logothetis, Nikos K; Platas-Iglesias, Carlos; Angelovski, Goran; Tóth, Éva

    2015-07-27

    A series of Gd(3+) complexes exhibiting a relaxometric response to zwitterionic amino acid neurotransmitters was synthesized. The design concept involves ditopic interactions 1) between a positively charged and coordinatively unsaturated Gd(3+) chelate and the carboxylate group of the neurotransmitters and 2) between an azacrown ether appended to the chelate and the amino group of the neurotransmitters. The chelates differ in the nature and length of the linker connecting the cyclen-type macrocycle that binds the Ln(3+) ion and the crown ether. The complexes are monohydrated, but they exhibit high proton relaxivities (up to 7.7 mM(-1)  s(-1) at 60 MHz, 310 K) due to slow molecular tumbling. The formation of ternary complexes with neurotransmitters was monitored by (1) H relaxometric titrations of the Gd(3+) complexes and by luminescence measurements on the Eu(3+) and Tb(3+) analogues at pH 7.4. The remarkable relaxivity decrease (≈80 %) observed on neurotransmitter binding is related to the decrease in the hydration number, as evidenced by luminescence lifetime measurements on the Eu(3+) complexes. These complexes show affinity for amino acid neurotransmitters in the millimolar range, which can be suited to imaging concentrations of synaptically released neurotransmitters. They display good selectivity over non-amino acid neurotransmitters (acetylcholine, serotonin, and noradrenaline) and hydrogenphosphate, but selectivity over hydrogencarbonate was not achieved.

  8. Gd3+-sensitive Na+ transport across the integument of Hirudo medicinalis.

    PubMed

    Schnizler, Mikael; Clauss, Wolfgang

    2003-01-01

    Leeches Hirudo medicinalis were exposed to either artificial pond water (APW; 1 mM NaCl) or to high-salinity conditions (HS; 200 mM NaCl) for several days. The aim of the study was to assess whether transepithelial ion conductances in their dorsal integuments were affected by this long-term acclimation. In voltage-clamp experiments using Ussing-type chambers, the transepithelial potential V(T) was clamped to 0 mV, and amiloride-sensitive currents (I(ami)) and total Na(+) transport (I(Na)) were determined. Apical Ca(2+)-free conditions strongly increased I(ami) to a similar magnitude in both differently acclimated integuments. Apical application of the lanthanide gadolinium <0.1 mM decreased the short-circuit current (I(sc)). In contrast, higher concentrations up to 10 mM Gd(3+) upregulated I(sc) by an additional 90% in APW integuments and by an additional 300% in HS integuments. This Gd(3+) effect was due to a doubling of I(Na) in APW and a more than sixfold increase of I(Na) in HS integuments. In summary, the macroscopic electrophysiological variables, including I(Na), were generally not affected by long-term exposure to high salinity. However, the presence of Gd(3+)-sensitive Na(+) conductances or regulating structures were greatly upregulated during HS acclimation.

  9. Approaches in the study of ganglioside metabolism

    SciTech Connect

    Tettamanti, G.; Ghidoni, R.; Sonnino, S.; Chigorno, V.; Venerando, B.; Giuliani, A.; Fiorilli, A.

    1984-01-01

    Ganglioside GM1, /sup 3/H-labeled in the sphingosine or terminal galactose moiety was injected into mice and its metabolic fate in the liver was followed. After administration of sphingosine-labeled GM1 all major liver gangliosides (GM3, GM2, GM1, GD1a-NeuAc, NeuG1) became radioactive, the radioactivity residing in all cases on the sphingosine moiety. The specific radioactivity was highest on GM1, followed by GM2, GM3 and GD1a-NeuAc, NeuG1. Several neutral glycosphingolipids and sphingomyelin were also formed. After administration of galactose-labelled GM1 the only radioactive gangliosides present in the liver were GM1 and GD1a-NeuAc, NeuG1, both carrying the radioactivity on the terminal galactose residue, with no formation of labelled neutral glycosphingolipids. Subcellular studies gave clear evidence that GM1, after being taken up by the liver, was mainly degraded to GM2, GM3 and neutral glycosphingolipids at the level of lysosomes. A part of it was sialylated to more complex gangliosides and some of its metabolic by-products were used for the biosynthesis of other sphingolipid species, likely at the level of the Golgi apparatus. All this suggests that exogenous GM1 is introduced in the metabolic routes of endogenous gangliosides and of other sphingolipids, which are operating in the liver.

  10. Tuning the selectivity of Gd3N cluster endohedral metallofullerene reactions with Lewis acids.

    PubMed

    Stevenson, Steven; Rottinger, Khristina A; Fahim, Muska; Field, Jessica S; Martin, Benjamin R; Arvola, Kristine D

    2014-12-15

    We demonstrate the manipulation of the Lewis acid strength to selectively fractionate different types of Gd3N metallofullerenes that are present in complex mixtures. Carbon disulfide is used for all Lewis acid studies. CaCl2 exhibits the lowest reactivity but the highest selectivity by precipitating only those gadolinium metallofullerenes with the lowest first oxidation potentials. ZnCl2 selectively complexes Gd3N@C88 during the first 4 h of reaction. Reaction with ZnCl2 for an additional 7 days permits a selective precipitation of Gd3N@C84 as the dominant endohedral isolated. A third fraction is the filtrate, which possesses Gd3N@C86 and Gd3N@C80 as the two dominant metallofullerenes. The order of increasing reactivity and decreasing selectivity (left to right) is as follows: CaCl2 < ZnCl2 < NiCl2 < MgCl2 < MnCl2 < CuCl2 < WCl4 ≪ WCl6 < ZrCl4 < AlCl3 < FeCl3. As a group, CaCl2, ZnCl2, and NiCl2 are the weakest Lewis acids and have the highest selectivity because of their very low precipitation onsets, which are below +0.19 V (i.e., endohedrals with first oxidation potentials below +0.19 V are precipitated). For CaCl2, the precipitation threshold is estimated at a remarkably low value of +0.06 V. Because most endohedrals possess first oxidation potentials significantly higher than +0.06 V, CaCl2 is especially useful in its ability to precipitate only a select group of gadolinium metallofullerenes. The Lewis acids of intermediate reactivity (i.e., precipitation onsets estimated between +0.19 and +0.4 V) are MgCl2, MnCl2, CuCl2, and WCl4. The strongest Lewis acids (WCl6, ZrCl4, AlCl3, and FeCl3) are the least selective and tend to precipitate the entire family of gadolinium metallofullerenes. Tuning the Lewis acid for a specific type of endohedral should be useful in a nonchromatographic purification method. The ability to control which metallofullerenes are permitted to precipitate and which endohedrals would remain in solution is a key outcome of this work.

  11. Gangliosides, or sialic acid, antagonize ethanol intoxication

    SciTech Connect

    Klemm, W.R.; Boyles, R.; Matthew, J.; Cherian, L.

    1988-01-01

    Because ethanol elicits a dose-dependent hydrolysis of brain sialogangliosides, the authors tested the possibility that injected gangliosides might antagonize intoxicating doses of ethanol. Clear anti-intoxication effects were seen at 24 hr post-injection of mixed mouse-brain gangliosides at 125-130 mg/kg, but not at lower or higher doses. Sleep time was reduced on the order of 50%, and roto-rod agility was significantly enhanced. Sialic acid (SA) similarly antagonized ethanol; however, the precursor of SA, N-acetyl-D-mannosamine, as well as ceramide and asialoganglioside did not.

  12. Recombination luminescence of CaSO4:Tb3+ and CaSO4:Gd3+phosphors

    NASA Astrophysics Data System (ADS)

    Kudryavtseva, Irina; Lushchik, Aleksandr; Maaroos, Aarne; Azmaganbetova, Zhannur; Nurakhmetov, Turlybek; Salikhoja, Zhussupbek

    2012-08-01

    A comparative study of the excitation of luminescence by VUV radiation as well as of thermally and photostimulated luminescence has been carried out for CaSO4:Tb3+ and CaSO4:Gd3+ phosphors, where Na+ or F- ions are used for charge compensation. The distinction in hole processes for the phosphors with Na+ or F- compensators is determined by the differing thermal stability of the holes localized at/near Tb3+Na+ and Gd3+Na+ (up to 100-160 K) or at/near Tb3+F- V Ca and Gd3+F- V Ca centers involving also a cation vacancy (up to 400-550 K). Tunnel luminescence in the pairs of localized electrons and holes nearby Tb3+ or Gd3+ has been detected. The mechanisms of electron-hole, hole-electron and tunnel recombination luminescence as well as a subsequent released energy transfer to RE3+ ions are considered.

  13. Investigation of Gd3N@C2n (40 <= n <= 44) family by Raman and inelastic electron tunneling spectroscopy

    NASA Astrophysics Data System (ADS)

    Burke, Brian; Chan, Jack; Williams, Keith; Ge, Jiechao; Shu, Chunying; Fu, Wujun; Dorn, Harry; Kushmerick, James; Puretzky, Alexander; Geohegan, David

    2010-03-01

    The structure and vibrational spectrum of Gd3N@C80 is studied through Raman and inelastic electron tunneling spectroscopy (IETS) as well as density functional theory (DFT) and universal force field (UFF) calculations. Hindered rotations, shown by both theory and experiment, indicate the formation of a Gd3N-C80 bond which reduces the ideal icosahedral symmetry of the C80 cage. The vibrational modes involving the movement of the encapsulated species are a fingerprint of the interaction between the fullerene cage and the core complex. We present Raman data for the Gd3N@C2n (40 <= n <= 44) family as well as Y3N@C80, Lu3N@C80, and Y3N@C88 for comparison. Conductance measurements have been performed on Gd3N@C80 and reveal a Kondo effect similar to that observed in C60.

  14. Ganglioside-magnetosome complex formation enhances uptake of gangliosides by cells

    PubMed Central

    Guan, Feng; Li, Xiang; Guo, Jia; Yang, Ganglong; Li, Xiang

    2015-01-01

    Bacterial magnetosomes, because of their nano-scale size, have a large surface-to-volume ratio and are able to carry large quantities of bioactive substances such as enzymes, antibodies, and genes. Gangliosides, a family of sialic acid-containing glycosphingolipids, function as distinctive cell surface markers and as specific determinants in cellular recognition and cell-to-cell communication. Exogenously added gangliosides are often used to study biological functions, transport mechanisms, and metabolism of their endogenous counterparts. Absorption of gangliosides into cells is typically limited by their tendency to aggregate into micelles in aqueous media. We describe here a simple strategy to remove proteins from the magnetosome membrane by sodium dodecyl sulfate treatment, and efficiently immobilize a ganglioside (GM1 or GM3) on the magnetosome by mild ultrasonic treatment. The maximum of 11.7±1.2 µg GM1 and 11.6±1.5 μg GM3 was loaded onto 1 mg magnetosome, respectively. Complexes of ganglioside-magnetosomes stored at 4°C for certain days presented the consistent stability. The use of GM1-magnetosome complex resulted in the greatest enhancement of ganglioside incorporation by cells. GM3-magnetosome complex significantly inhibited EGF-induced phosphorylation of the epidermal growth factor receptor. Both of these effects were further enhanced by the presence of a magnetic field. PMID:26609230

  15. Ganglioside-magnetosome complex formation enhances uptake of gangliosides by cells.

    PubMed

    Guan, Feng; Li, Xiang; Guo, Jia; Yang, Ganglong; Li, Xiang

    2015-01-01

    Bacterial magnetosomes, because of their nano-scale size, have a large surface-to-volume ratio and are able to carry large quantities of bioactive substances such as enzymes, antibodies, and genes. Gangliosides, a family of sialic acid-containing glycosphingolipids, function as distinctive cell surface markers and as specific determinants in cellular recognition and cell-to-cell communication. Exogenously added gangliosides are often used to study biological functions, transport mechanisms, and metabolism of their endogenous counterparts. Absorption of gangliosides into cells is typically limited by their tendency to aggregate into micelles in aqueous media. We describe here a simple strategy to remove proteins from the magnetosome membrane by sodium dodecyl sulfate treatment, and efficiently immobilize a ganglioside (GM1 or GM3) on the magnetosome by mild ultrasonic treatment. The maximum of 11.7±1.2 µg GM1 and 11.6±1.5 μg GM3 was loaded onto 1 mg magnetosome, respectively. Complexes of ganglioside-magnetosomes stored at 4°C for certain days presented the consistent stability. The use of GM1-magnetosome complex resulted in the greatest enhancement of ganglioside incorporation by cells. GM3-magnetosome complex significantly inhibited EGF-induced phosphorylation of the epidermal growth factor receptor. Both of these effects were further enhanced by the presence of a magnetic field.

  16. Zero field splitting fluctuations induced phase relaxation of Gd3+ in frozen solutions at cryogenic temperatures

    NASA Astrophysics Data System (ADS)

    Raitsimring, A.; Dalaloyan, A.; Collauto, A.; Feintuch, A.; Meade, T.; Goldfarb, D.

    2014-11-01

    Distance measurements using double electron-electron resonance (DEER) and Gd3+ chelates for spin labels (GdSL) have been shown to be an attractive alternative to nitroxide spin labels at W-band (95 GHz). The maximal distance that can be accessed by DEER measurements and the sensitivity of such measurements strongly depends on the phase relaxation of Gd3+ chelates in frozen, glassy solutions. In this work, we explore the phase relaxation of Gd3+-DOTA as a representative of GdSL in temperature and concentration ranges typically used for W-band DEER measurements. We observed that in addition to the usual mechanisms of phase relaxation known for nitroxide based spin labels, GdSL are subjected to an additional phase relaxation mechanism that features an increase in the relaxation rate from the center to the periphery of the EPR spectrum. Since the EPR spectrum of GdSL is the sum of subspectra of the individual EPR transitions, we attribute this field dependence to transition dependent phase relaxation. Using simulations of the EPR spectra and its decomposition into the individual transition subspectra, we isolated the phase relaxation of each transition and found that its rate increases with |ms|. We suggest that this mechanism is due to transient zero field splitting (tZFS), where its magnitude and correlation time are scaled down and distributed as compared with similar situations in liquids. This tZFS induced phase relaxation mechanism becomes dominant (or at least significant) when all other well-known phase relaxation mechanisms, such as spectral diffusion caused by nuclear spin diffusion, instantaneous and electron spin spectral diffusion, are significantly suppressed by matrix deuteration and low concentration, and when the temperature is sufficiently low to disable spin lattice interaction as a source of phase relaxation.

  17. Zero field splitting fluctuations induced phase relaxation of Gd3+ in frozen solutions at cryogenic temperatures

    PubMed Central

    Raitsimring, A.; Dalaloyan, A.; Collauto, A.; Feintuch, A.; Meade, T.; Goldfarb, D.

    2015-01-01

    Distance measurements using double electron–electron resonance (DEER) and Gd3+ chelates for spin labels (GdSL) have been shown to be an attractive alternative to nitroxide spin labels at W-band (95 GHz). The maximal distance that can be accessed by DEER measurements and the sensitivity of such measurements strongly depends on the phase relaxation of Gd3+ chelates in frozen, glassy solutions. In this work, we explore the phase relaxation of Gd3+-DOTA as a representative of GdSL in temperature and concentration ranges typically used for W-band DEER measurements. We observed that in addition to the usual mechanisms of phase relaxation known for nitroxide based spin labels, GdSL are subjected to an additional phase relaxation mechanism that features an increase in the relaxation rate from the center to the periphery of the EPR spectrum. Since the EPR spectrum of GdSL is the sum of subspectra of the individual EPR transitions, we attribute this field dependence to transition dependent phase relaxation. Using simulations of the EPR spectra and its decomposition into the individual transition subspectra, we isolated the phase relaxation of each transition and found that its rate increases with |ms|. We suggest that this mechanism is due to transient zero field splitting (tZFS), where its magnitude and correlation time are scaled down and distributed as compared with similar situations in liquids. This tZFS induced phase relaxation mechanism becomes dominant (or at least significant) when all other well-known phase relaxation mechanisms, such as spectral diffusion caused by nuclear spin diffusion, instantaneous and electron spin spectral diffusion, are significantly suppressed by matrix deuteration and low concentration, and when the temperature is sufficiently low to disable spin lattice interaction as a source of phase relaxation. PMID:25442776

  18. Zero field splitting fluctuations induced phase relaxation of Gd3+ in frozen solutions at cryogenic temperatures.

    PubMed

    Raitsimring, A; Dalaloyan, A; Collauto, A; Feintuch, A; Meade, T; Goldfarb, D

    2014-11-01

    Distance measurements using double electron-electron resonance (DEER) and Gd(3+) chelates for spin labels (GdSL) have been shown to be an attractive alternative to nitroxide spin labels at W-band (95GHz). The maximal distance that can be accessed by DEER measurements and the sensitivity of such measurements strongly depends on the phase relaxation of Gd(3+) chelates in frozen, glassy solutions. In this work, we explore the phase relaxation of Gd(3+)-DOTA as a representative of GdSL in temperature and concentration ranges typically used for W-band DEER measurements. We observed that in addition to the usual mechanisms of phase relaxation known for nitroxide based spin labels, GdSL are subjected to an additional phase relaxation mechanism that features an increase in the relaxation rate from the center to the periphery of the EPR spectrum. Since the EPR spectrum of GdSL is the sum of subspectra of the individual EPR transitions, we attribute this field dependence to transition dependent phase relaxation. Using simulations of the EPR spectra and its decomposition into the individual transition subspectra, we isolated the phase relaxation of each transition and found that its rate increases with |ms|. We suggest that this mechanism is due to transient zero field splitting (tZFS), where its magnitude and correlation time are scaled down and distributed as compared with similar situations in liquids. This tZFS induced phase relaxation mechanism becomes dominant (or at least significant) when all other well-known phase relaxation mechanisms, such as spectral diffusion caused by nuclear spin diffusion, instantaneous and electron spin spectral diffusion, are significantly suppressed by matrix deuteration and low concentration, and when the temperature is sufficiently low to disable spin lattice interaction as a source of phase relaxation. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Structural and dc electrical resistivity study of Gd 3+-substituted Cu-Cd mixed ferrites

    NASA Astrophysics Data System (ADS)

    Kolekar, C. B.; Kamble, P. N.; Vaingankar, A. S.

    1994-11-01

    Polycrystalline ferrite compositions of Cd xCu 1- xFe 2- yGd yO 4 ( x = 0.0, 0.2, 0.4, 0.6, 0.8, and 1.0; y = 0.0 and 0.1) were prepared by the standard ceramic technique. The X-ray crystallographic study was done using filtered Cu K α radiation. From the diffractograms it is observed that for x ⩾ 0.2 compounds are cubic spinels, while for x = 0 they are tetragonal, and the dependence of the lattice constant on cadmium concentration obeys Vegard's law. The infrared absorption of the powder samples shows two strong absorption bands in the frequency range 400-600 cm -1, and the analysis shows that Gd occupies 'B' sites. The chemical analysis was done by atomic absorption spectroscopy. The dc resistivity study shows an increase in Δ E values and thus in the resistivity after Gd 3+ substitution, suggesting that even though Gd 3+ occupies 'B' sites it does not take part in the conduction mechanism, but impedes it.

  20. Ganglioside-Lipid and Ganglioside-Protein Interactions Revealed by Coarse-Grained and Atomistic Molecular Dynamics Simulations

    PubMed Central

    2016-01-01

    Gangliosides are glycolipids in which an oligosaccharide headgroup containing one or more sialic acids is connected to a ceramide. Gangliosides reside in the outer leaflet of the plasma membrane and play a crucial role in various physiological processes such as cell signal transduction and neuronal differentiation by modulating structures and functions of membrane proteins. Because the detailed behavior of gangliosides and protein-ganglioside interactions are poorly known, we investigated the interactions between the gangliosides GM1 and GM3 and the proteins aquaporin (AQP1) and WALP23 using equilibrium molecular dynamics simulations and potential of mean force calculations at both coarse-grained (CG) and atomistic levels. In atomistic simulations, on the basis of the GROMOS force field, ganglioside aggregation appears to be a result of the balance between hydrogen bond interactions and steric hindrance of the headgroups. GM3 clusters are slightly larger and more ordered than GM1 clusters due to the smaller headgroup of GM3. The different structures of GM1 and GM3 clusters from atomistic simulations are not observed at the CG level based on the Martini model, implying a difference in driving forces for ganglioside interactions in atomistic and CG simulations. For protein-ganglioside interactions, in the atomistic simulations, GM1 lipids bind to specific sites on the AQP1 surface, whereas they are depleted from WALP23. In the CG simulations, the ganglioside binding sites on the AQP1 surface are similar, but ganglioside aggregation and protein-ganglioside interactions are more prevalent than in the atomistic simulations. Using the polarizable Martini water model, results were closer to the atomistic simulations. Although experimental data for validation is lacking, we proposed modified Martini parameters for gangliosides to more closely mimic the sizes and structures of ganglioside clusters observed at the atomistic level. PMID:27610460

  1. Postnatal dietary supplementation with either gangliosides or choline: effects on spatial short-term memory in artificially-reared rats.

    PubMed

    Wainwright, Patricia E; Lomanowska, Anna M; McCutcheon, Dawn; Park, Eek J; Clandinin, M Thomas; Ramanujam, Kalathur S

    2007-01-01

    This study addressed the hypothesis that dietary supplementation with either gangliosides or choline during the brain growth spurt would enhance short-term spatial memory. Male Long-Evans rats were reared artificially from postnatal days (PD) 5-18 and were fed diets containing either (i) choline chloride 1250 mg/l (CHL), (ii) choline chloride 250 mg/l and GD3 24 mg/l (GNG) or (iii) choline chloride 250 mg/l (STD). A fourth group (SCK) was reared normally. Rats were weaned onto AIN 93G diet and on PD 35 were trained on a cued delayed- matching-to-place version of the Morris water maze. All groups learned to swim to the beacon that indicated the platform position on the first trial; similarly, on the second un-cued trial, the distance swam to reach the platform decreased to the same extent in all groups over the five days of training. The groups also responded in the same way to an increase in delay between the first and second trial from 1 min to 1 h, showing an increase in the distance swam, accompanied by a decrease in the number of direct swims to the platform. Thus, all rats were equally proficient at using spatial short-term memory, regardless of the choline or ganglioside content of the preweaning diet.

  2. Inhibitory effect of ganglioside GD1b on K+ current in hippocampal neurons and its involvement in apoptosis suppression.

    PubMed

    Chen, Xuesong; Chi, Shaopeng; Liu, Mingna; Yang, Wei; Wei, Taotao; Qi, Zhi; Yang, Fuyu

    2005-12-01

    Gangliosides are endogenous membrane components enriched in neuronal cells. They have been shown to play regulatory roles in many cellular processes. Here, we show for the first time that ganglioside GD1b plays an antiapoptotic role in cultured hippocampal neurons. GD1b inhibited the voltage-dependent outward delayed rectifier current (I(K)) but not the transient outward A-type current in a dose-dependent manner, with an IC50 value of 15.2 microM. This effect appears to be somehow specific, because GD1b, but not GM1, GM2, GM3, GD1a, GD3, or GT1b, was effective in inhibiting I(K). Intracellular application of staurosporine (STS; 0.1 microM) resulted in rapid activation of I(K), which was partially reversed upon addition of the K+ channel blocker tetraethylammonium (TEA; 5 mM) and GD1b (10 microM). Furthermore, GD1b (10 microM) attenuated STS-induced neuronal apoptosis by nearly the same amount as 5 mM TEA. In addition, GD1b suppressed the apoptosis-associated caspase 3 activation that was activated by STS. Collectively, these findings suggest that GD1b plays an antiapoptotic role in cultured hippocampal neurons through its inhibitory effect on the I(K) and caspase activity.

  3. Influence of Gd3+ concentration on luminescence properties of Eu3+ ions in sol-gel materials

    NASA Astrophysics Data System (ADS)

    Szpikowska-Sroka, Barbara; Pawlik, Natalia; Pisarski, Wojciech A.

    2016-12-01

    The sol-gel powders doubly-doped with Gd3+/Eu3+ ions with different concentration of Gd3+ have been successfully obtained. The spectroscopic characterization of prepared samples was conducted based on excitation and emission spectra as well as luminescence decay analysis. Upon direct excitation of Eu3+ active ions, the characteristic 5D0 → 7F1 (orange) and 5D0 → 7F2 (red) emission bands were observed. The energy transfer from Gd3+ to Eu3+ ions was registered upon λexc = 273 nm excitation. An efficient conversion of ultraviolet radiation (UV) into visible luminescence was successfully observed. The energy transfer process from Gd3+ to Eu3+ led to longer luminescence decay from the 5D0 state in comparison to that obtained under direct excitation of Eu3+ ions (λexc = 393 nm). Generally, obtained results clearly indicated the beneficial influence of increasing concentration of Gd3+ ions on luminescence properties of Eu3+ in studied silica sol-gel phosphors.

  4. Synthesis, complexation and NMR relaxation properties of Gd3+ complexes of Mes(DO3A)3.

    PubMed

    Miéville, Pascal; Jaccard, Hugues; Reviriego, Felipe; Tripier, Raphaël; Helm, Lothar

    2011-04-28

    Medium sized molecules endowed with multiple Gd(3+) complexes are efficient high magnetic field MRI contrast agents. The novel ligand Mes(DO3A)(3), presenting three DO3A (1,4,7,10-tetraazacyclododecane-N,N',N''-triacetatic acid) units grafted on the methyl positions of a central mesitylene (1,3,5-trimethylbenzene), has been synthesized. Designed as an MRI contrast agent, this ligand is complexed with Gd(3+) and its efficiency is characterized by variable field (1)H-NMR and variable temperature (17)O-NMR. The evaluation of the relaxation and paramagnetic chemical shift data allowed the identification of an undesired binuclear complex which is obtained by using the classical procedure for complexation as described in the literature. An intramolecular capping mechanism appears to be responsible for the failure to introduce a third Gd(3+) ion into the ligand. A new alternative method, based on pre-complexation with Mg(2+) followed by transmetallation is described here and leads to the expected trinuclear Gd(3+) complex [Mes{Gd(DO3A)(H(2)O)(2)}(3)]. The rate constants for the water exchange (k(ex)(298) = 32 × 10(6) s(-1)) for the bi- and trinuclear complex appeared to be the same, which is surprising in relation to the difference in the charge of the complex and to the difference in the number of coordinated water molecules, one and two per Gd(3+) for the binuclear and trinuclear complex, respectively.

  5. The Pathogenic Role of Ganglioside Metabolism in Alzheimer's Disease-Cholinergic Neuron-Specific Gangliosides and Neurogenesis.

    PubMed

    Ariga, Toshio

    2017-01-01

    Alzheimer's disease (AD) is the most common type of dementia with clinical symptoms that include deficits in memory, judgment, thinking, and behavior. Gangliosides are present on the outer surface of plasma membranes and are especially abundant in the nervous tissues of vertebrates. Ganglioside metabolism, especially the cholinergic neuron-specific gangliosides, GQ1bα and GT1aα, is altered in mouse model of AD and patients with AD. Thus, alterations in ganglioside metabolism may participate in several events related to the pathogenesis of AD. Increased expressions of GT1aα may reflect cholinergic neurogenesis. Most changes in ganglioside metabolism occur in the specific brain areas and their lipid rafts. Targeting ganglioside metabolism in lipid rafts may represent an underexploited opportunity to design novel therapeutic strategies for AD.

  6. Brain gangliosides in the presenile dementia of Pick.

    PubMed Central

    Kamp, P E; den Hartog Jager, W A; Maathuis, J; de Groot, P A; de Jong, J M; Bolhuis, P A

    1986-01-01

    Histochemical analysis of frontal and temporal lobes from four patients with Pick presenile dementia indicated intracellular and extracellular deposits of gangliosides. Thin layer chromatography of gangliosides disclosed the presence of an unknown ganglioside, a decrease of N-acetylgalactosamine-GDla and an increase of GTla and/or GD2 in white matter of Pick brain. Chromatography of gray matter and quantitation of the sialic acid content yielded results similar to controls. It is suggested that degradation and removal of gangliosides is incomplete in Pick disease. Images PMID:3746324

  7. Anchored and soluble gangliosides contribute to myelosupportivity of stromal cells

    SciTech Connect

    Ziulkoski, Ana L.; Santos, Aline X.S. dos; Andrade, Claudia M.B.; Trindade, Vera M.T.; Daniotti, Jose Luis; Borojevic, Radovan; Guma, Fatima C.R.

    2009-10-09

    Stroma-mediated myelopoiesis depends upon growth factors and an appropriate intercellular microenvironment. Previous studies have demonstrated that gangliosides, produced by hepatic stromal cell types, are required for optimal myelosupportive function. Here, we compared the mielossuportive functions of a bone marrow stroma (S17) and skin fibroblasts (SF) regarding their ganglioside pattern of synthesis and shedding. The survival and proliferation of a myeloid precursor cell (FDC-P1) were used as reporter. Although the ganglioside synthesis of the two stromal cells was similar, their relative content and shedding were distinct. The ganglioside requirement for mielossuportive function was confirmed by the decreased proliferation of FDC-P1 cells in ganglioside synthesis-inhibited cultures and in presence of an antibody to GM3 ganglioside. The distinct mielossuportive activities of the S17 and SF stromata may be related to differences on plasma membrane ganglioside concentrations or to differences on the gangliosides shed and their subsequent uptake by myeloid cells, specially, GM3 ganglioside.

  8. Gangliosides Have a Functional Role during Rotavirus Cell Entry

    PubMed Central

    Martínez, Miguel Angel; López, Susana; Arias, Carlos F.

    2013-01-01

    Cell entry of rotaviruses is a complex process, which involves sequential interactions with several cell surface molecules. Among the molecules implicated are gangliosides, glycosphingolipids with one or more sialic acid (SA) residues. The role of gangliosides in rotavirus cell entry was studied by silencing the expression of two key enzymes involved in their biosynthesis—the UDP-glucose:ceramide glucosyltransferase (UGCG), which transfers a glucose molecule to ceramide to produce glucosylceramide GlcCer, and the lactosyl ceramide-α-2,3–sialyl transferase 5 (GM3-s), which adds the first SA to lactoceramide-producing ganglioside GM3. Silencing the expression of both enzymes resulted in decreased ganglioside levels (as judged by GM1a detection). Four rotavirus strains tested (human Wa, simian RRV, porcine TFR-41, and bovine UK) showed a decreased infectivity in cells with impaired ganglioside synthesis; however, their replication after bypassing the entry step was not affected, confirming the importance of gangliosides for cell entry of the viruses. Interestingly, viral binding to the cell surface was not affected in cells with inhibited ganglioside synthesis, but the infectivity of all strains tested was inhibited by preincubation of gangliosides with virus prior to infection. These data suggest that rotaviruses can attach to cell surface in the absence of gangliosides but require them for productive cell entry, confirming their functional role during rotavirus cell entry. PMID:23135722

  9. Gangliosides have a functional role during rotavirus cell entry.

    PubMed

    Martínez, Miguel Angel; López, Susana; Arias, Carlos F; Isa, Pavel

    2013-01-01

    Cell entry of rotaviruses is a complex process, which involves sequential interactions with several cell surface molecules. Among the molecules implicated are gangliosides, glycosphingolipids with one or more sialic acid (SA) residues. The role of gangliosides in rotavirus cell entry was studied by silencing the expression of two key enzymes involved in their biosynthesis--the UDP-glucose:ceramide glucosyltransferase (UGCG), which transfers a glucose molecule to ceramide to produce glucosylceramide GlcCer, and the lactosyl ceramide-α-2,3-sialyl transferase 5 (GM3-s), which adds the first SA to lactoceramide-producing ganglioside GM3. Silencing the expression of both enzymes resulted in decreased ganglioside levels (as judged by GM1a detection). Four rotavirus strains tested (human Wa, simian RRV, porcine TFR-41, and bovine UK) showed a decreased infectivity in cells with impaired ganglioside synthesis; however, their replication after bypassing the entry step was not affected, confirming the importance of gangliosides for cell entry of the viruses. Interestingly, viral binding to the cell surface was not affected in cells with inhibited ganglioside synthesis, but the infectivity of all strains tested was inhibited by preincubation of gangliosides with virus prior to infection. These data suggest that rotaviruses can attach to cell surface in the absence of gangliosides but require them for productive cell entry, confirming their functional role during rotavirus cell entry.

  10. Anchored and soluble gangliosides contribute to myelosupportivity of stromal cells.

    PubMed

    Ziulkoski, Ana L; dos Santos, Aline X S; Andrade, Cláudia M B; Trindade, Vera M T; Daniotti, José Luis; Borojevic, Radovan; Guma, Fátima C R

    2009-10-09

    Stroma-mediated myelopoiesis depends upon growth factors and an appropriate intercellular microenvironment. Previous studies have demonstrated that gangliosides, produced by hepatic stromal cell types, are required for optimal myelosupportive function. Here, we compared the mielossuportive functions of a bone marrow stroma (S17) and skin fibroblasts (SF) regarding their ganglioside pattern of synthesis and shedding. The survival and proliferation of a myeloid precursor cell (FDC-P1) were used as reporter. Although the ganglioside synthesis of the two stromal cells was similar, their relative content and shedding were distinct. The ganglioside requirement for mielossuportive function was confirmed by the decreased proliferation of FDC-P1 cells in ganglioside synthesis-inhibited cultures and in presence of an antibody to GM3 ganglioside. The distinct mielossuportive activities of the S17 and SF stromata may be related to differences on plasma membrane ganglioside concentrations or to differences on the gangliosides shed and their subsequent uptake by myeloid cells, specially, GM3 ganglioside.

  11. Temperature-stabilized optical isolator for collimated light using (BiLuGd)(3)Fe(5)O(12)/(BiGd)(3)(FeGa)(5)O(12) composite film.

    PubMed

    Matsuda, K; Mlnernoto, H; Kamada, O; Ishlzuka, S

    1988-04-01

    We have fabricated optical isolators whose temperature dependence of the isolation ratio has a stability of <0.2 dB using (BiLuGd)(3)Fe(5)O(12)/(BiGd)(3)(FeGa)(5)0(12) composite film. It has been confirmed that the temperature-dependent forward loss of the isolators originates from the thermal fluctuation of the absorption peak in the films. We have also evaluated the degradation of the isolation ratio for collimated light depending on the incident angle of the collimated light, the incident position with respect to the optic axis, and the wavelength range needed for practical use.

  12. The role of gangliosides in neurodevelopment.

    PubMed

    Palmano, Kate; Rowan, Angela; Guillermo, Rozey; Guan, Jian; McJarrow, Paul

    2015-05-22

    Gangliosides are important components of neuronal cell membranes and it is widely accepted that they play a critical role in neuronal and brain development. They are functionally involved in neurotransmission and are thought to support the formation and stabilization of functional synapses and neural circuits required as the structural basis of memory and learning. Available evidence, as reviewed herein, suggests that dietary gangliosides may impact positively on cognitive functions, particularly in the early postnatal period when the brain is still growing. Further, new evidence suggests that the mechanism of action may be through an effect on the neuroplasticity of the brain, mediated through enhanced synaptic plasticity in the hippocampus and nigro-striatal dopaminergic pathway.

  13. The Role of Gangliosides in Neurodevelopment

    PubMed Central

    Palmano, Kate; Rowan, Angela; Guillermo, Rozey; Guan, Jian; Mc Jarrow, Paul

    2015-01-01

    Gangliosides are important components of neuronal cell membranes and it is widely accepted that they play a critical role in neuronal and brain development. They are functionally involved in neurotransmission and are thought to support the formation and stabilization of functional synapses and neural circuits required as the structural basis of memory and learning. Available evidence, as reviewed herein, suggests that dietary gangliosides may impact positively on cognitive functions, particularly in the early postnatal period when the brain is still growing. Further, new evidence suggests that the mechanism of action may be through an effect on the neuroplasticity of the brain, mediated through enhanced synaptic plasticity in the hippocampus and nigro-striatal dopaminergic pathway. PMID:26007338

  14. Angle-Dependent Microresonator ESR Characterization of Locally Doped Gd3 + :Al2O3

    NASA Astrophysics Data System (ADS)

    Wisby, I. S.; de Graaf, S. E.; Gwilliam, R.; Adamyan, A.; Kubatkin, S. E.; Meeson, P. J.; Tzalenchuk, A. Ya.; Lindström, T.

    2016-08-01

    Interfacing rare-earth-doped crystals with superconducting circuit architectures provides an attractive platform for quantum memory and transducer devices. Here, we present the detailed characterization of such a hybrid system: a locally implanted rare-earth Gd3 + in Al2O3 spin system coupled to a superconducting microresonator. We investigate the properties of the implanted spin system through angular-dependent microresonator electron spin resonance (micro-ESR) spectroscopy. We find, despite the high-energy near-surface implantation, the resulting micro-ESR spectra to be in excellent agreement with the modeled Hamiltonian, supporting the integration of dopant ions into their relevant lattice sites while maintaining crystalline symmetries. Furthermore, we observe clear contributions from individual microwave field components of our microresonator, emphasizing the need for controllable local implantation.

  15. Enhanced magnetodielectricity in Gd3+ substituted Bi2Fe4O9 ceramics

    NASA Astrophysics Data System (ADS)

    Mohapatra, S. R.; Yadav, C. S.; Kaushik, S. D.; Singh, A. K.

    2017-05-01

    We report the synthesis of orthorhombic Bi2(1-x)Gd2xFe4O9 (x=0, 0.015) ceramics by solid state route and have investigated its structural, magnetic, dielectric and magnetodielectric properties. Rietveld refinement of X-ray diffraction pattern at room temperature shows structural distortion due to lower ionic radii substitution. Magnetic measurements confirmed an enhanced antiferromagnetic transition temperature (TN) in x = 0.015 (254 K) as compared to the parent sample (250 K) along with an increase in magnetization due to the coupling between Gd3+ and Fe3+ ions. A concomitant anomaly in dielectric (ɛ') and tan loss plot around TN indicated plausible magnetoelectric coupling (MEC) in both the samples and the MEC coefficient (γ) is approximated by ˜ γM2. The highest value of the magnetodielectric response (˜ 100% enhancement) has been observed for x=0.015 sample.

  16. Enhanced relaxivity of Gd3+-based contrast agents geometrically confined within porous nanoconstructs

    PubMed Central

    Sethi, Richa; Ananta, Jeyarama S.; Karmonik, Christof; Zhong, Meng; Fung, Steve H.; Liu, Xuewu; Li, King; Ferrari, Mauro; Wilson, Lon J.; Decuzzi, Paolo

    2013-01-01

    Gadolinium chelates, which are currently approved for clinical MRI use, provide relaxivities well below their theoretical limit, and they also lack tissue specificity. Recently, the geometrical confinement of Gd3+-based contrast agents (CAs) within porous structures has been proposed as a novel, alternative strategy to improve relaxivity without chemical modification of the CA. Here, we have characterized and optimized the performance of MRI nanoconstructs obtained by loading [Gd(DTPA)(H2O)]2− (Magnevist®) into the pores of injectable mesoporous silicon particles. Nanoconstructs with three different pore sizes were studied, and at 60 MHz, they exhibited longitudinal relaxivities of ~ 24 mM−1s−1 for 5 – 10 nm pores and ~ 10 mM−1s−1 for 30 – 40 nm pores. No enhancement in relaxivity was observed for larger pores sizes. Using an outer-sphere compound, [GdTTHA]−3, and mathematical modeling, it was demonstrated that the relaxivity enhancement is due to the increase in rotational correlation times (CA adsorbed on the pore walls) and diffusion correlation times (reduced mobility of the water molecules), as the pore sizes decreases. It was also observed that extensive CA adsorption on the outer surface of the silicon particles negates the advantages offered by nanoscale confinement. Upon incubation with HeLa cells, the nanoconstructs did not demonstrate significant cytotoxicity for up to 3 days post incubation, at different particle/cell ratios. In addition, the nanoconstructs showed complete degradation after 24h of continuous agitation in PBS. These data support and confirm the hypothesis that the geometrical confinement of Gd3+-chelate compounds into porous structures offers MRI nanoconstructs with enhanced relaxivity (up to 6 times for [Gd(DTPA)(H2O)]2−, and 4 times for [GdTTHA]−3) and, potentially, improved stability, reduced toxicity and tissue specificity. PMID:22991316

  17. Mapping of second-nearest-neighbor fluoride ions of orthorhombic Gd 3+-Ag + complexes in CaF 2

    NASA Astrophysics Data System (ADS)

    Nakata, R.; Den Hartog, H. W.

    The ENDOR technique is applied to determine the positions of 24 second-nearest-neighbor F - ions around an orthorhombic Gd 3+-Ag + complex in CaF 2 crystals. Experimental ENDOR data of the second-nearest-neighbor F - ions are analyzed by using the usual spin Hamiltonian and a least-squares fitting method. The best fits of the experimental results give superhyperfine (shf) constants and the F - directions ( K, L, M) with respect to the Gd 3+ ion, from which the distance between the second-nearest-neighbor F - ion and the Gd 3+ ion is determined by assuming that the hyperfine interaction is due to the classical dipole-dipole interaction. The displacements of the F - ions are estimated and compared with the theoretical values calculated by Bijvank and den Hartog on the basis of a polarizable point charge model.

  18. Effects of Gd3+ modifications on the photoelectrochemical properties of TiO2-based dye-sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Qu, Xiaofei; Hou, Yuchen; Yang, Junying; Liu, Meihua; Shi, Liang; Du, Fanglin

    2017-05-01

    In this paper, TiO2 particles ( 30 nm) modified with Gd2O3-coating layer ( 2 nm) for dye-sensitized solar cells (DSSCs) were fabricated via the hydrothermal method. Among the solar cells based on the Gd3+-doped TiO2 photoanodes, the optimal conversion efficiency was obtained from the 0.025Gd3+-modified TiO2-based cell, with a 17.7% improvement in the efficiency as compared to the unmodified one (7.18%). This enhancement was probably due to the improved UV radiation harvesting via a down-conversion luminescence process by Gd3+ ions, enhancement of visible light absorption and improved dye loading capacity. In addition, after Gd modification, a thin coating could be formed on the TiO2 nanoparticles, which worked as an energy barrier and resulted in a lower charge recombination.

  19. Effect of Gd3+ substitution on structural, magnetic, dielectric and optical properties of nanocrystalline CoFe2O4

    NASA Astrophysics Data System (ADS)

    Joshi, Seema; Kumar, Manoj; Chhoker, Sandeep; Kumar, Arun; Singh, Mahavir

    2017-03-01

    Nanoparticles of CoGdxFe2-xO4 with x=0.0, 0.03, 0.05, 0.07, 0.10 and 0.15 were synthesized by co-precipitation method. Gd3+ substitution effect on different properties of nanocrystalline CoFe2O4 has been studied. X-ray diffraction and Raman spectroscopy confirmed the formation of single phase cubic mixed spinel structure. Cation distribution has been proposed from Rietveld refined data. Mössbauer spectra at room temperature showed two ferrimagnetic Zeeman sextets with one superparamagnetic doublet. Mössbauer parameters suggested that Gd3+ ions occupy the octahedral site in CoFe2O4. Room temperature magnetic measurements exhibited that the saturation magnetization decreased from 91 emu/gm to 54 emu/gm for x=0.0 to 0.15 samples. The coercivity decreased from 1120 Oe to 340 Oe for x=0.0 to 0.07 samples and increased from 400 Oe to 590 Oe for x=0.10 and 0.15 samples, respectively. Raman analysis showed that the degree of inversion with Gd3+ substitution supporting the variation of coercivity. Electron spin resonance spectra revealed the dominancy of superexchange interactions in these samples. Optical band gap measurement suggested that all samples are indirect band gap materials and band gap has been decreased with Gd3+ substitution. Both dielectric constant and dielectric loss is found to decrease because of the decrease in hopping rate with the Gd3+ substitution for Fe3+ at the octahedral sites. Low dielectric loss suggested the applicability of Gd3+ doped CoFe2O4 nanoparticles for high frequency microwave device applications.

  20. Influence of Gd3+ co-doping on structural property of CaMoO4:Eu nanoparticles.

    PubMed

    Singh, B P; Parchur, A K; Ningthoujam, R S; Ansari, A A; Singh, P; Rai, S B

    2014-03-28

    A facile auto-combustion route is used for the synthesis of Gd(3+) (2, 5, 7 and 10 at%) co-doped CaMoO4:Eu nanoparticles. X-ray diffraction study suggests that as-prepared samples have extra impurity phases in addition to main tetragonal phase of CaMoO4, and such extra phases decrease as the annealing temperature increases from 600 to 900 °C. The crystal structure has been analysed using Rietveld program. It has space group I4₁/a (88) and Z = 4 (number of CaMoO4 formula units per unit cell). Average crystallite sizes of as-prepared, 600 and 900 °C annealed samples for 2 at% Gd(3+) are found to be ~33, 48 and 61 nm, respectively. The lattice strains of 5 at% Gd(3+) co-doped CaMoO4:Eu for as-prepared and 900 °C are 0.001 and 0.002, respectively. Fourier transform infrared spectroscopy gives the absorption bands at ~815 and 427 cm(-1), which are related to asymmetric stretching and bending vibrations of MoO4(2-) tetrahedron. Particle morphology is studied using scanning and transmission electron microscopy (SEM and TEM), and aggregation of particles is found. X-ray photoelectron spectroscopy (XPS) is utilized to examine the oxidation states of metal ions/oxygen and oxygen ion vacancies in Gd(3+) co-doped CaMoO4:Eu. With an increase in Gd(3+) concentration, peaks corresponding to the Gd(3+) (2p(3/2) and 2p(5/2)) binding energy could be detected.

  1. Coupling fast water exchange to slow molecular tumbling in Gd3+ chelates: why faster is not always better

    PubMed Central

    Avedano, Stefano; Botta, Mauro; Haigh, Julian S.; Longo, Dario; Woods, Mark

    2013-01-01

    The influence of dynamics on solution state structure is a widely overlooked consideration in chemistry. Variations in Gd3+ chelate hydration with changing coordination geometry and dissociative water exchange kinetics substantially impact the effectiveness (or relaxivity) of mono-hydrated Gd3+ chelates as T1-shortening contrast agents for MRI. Theory shows that relaxivity is highly dependent upon the Gd3+-water proton distance (rGdH) and yet this distance is almost never considered as a variable in assessing the relaxivity of a Gd3+ chelate as a potential contrast agent. The consequence of this omission can be seen when considering the relaxivity of isomeric Gd3+ chelates that exhibit different dissociative water exchange kinetics. The results described herein show that the relaxivity of a chelate with ‘optimal’ dissociative water exchange kinetics is actually lower than that of an isomeric chelate with ‘sub-optimal’ dissociative water exchange. When the rate of molecular tumbling of these chelates is slowed, an approach that has long been understood to increase relaxivity, the observed difference in relaxivity is increased with the more rapidly exchanging (‘optimal’) chelate exhibiting lower relaxivity than the ‘sub-optimally’ exchanging isomer. The difference between the chelates arises from a non-field dependent parameter: either the hydration number (q) or rGdH. For solution state Gd3+ chelates, changes in the values of q and rGdH are indistinguishable. These parametric expressions simply describe the hydration state of the chelate – i.e. the number and position of closely associating water molecules. The hydration state (q/rGdH6) of a chelate is intrinsically linked to its dissociative water exchange rate kex and the interrelation of these parameters must be considered when examining the relaxivity of Gd3+ chelates. The data presented herein indicates that the changes in the hydration parameter (q/rGdH6) associated with changing dissociative

  2. Fluorescent gangliosides as probes for the retention and organization of fibronectin by ganglioside-deficient mouse cells

    PubMed Central

    1985-01-01

    Ganglioside-deficient transformed mouse fibroblasts (NCTC 2071A cells), which grow in serum-free medium, synthesize fibronectin but do not retain it on the cell surface. When fluorescent derivatives of gangliosides, containing either rhodamine or Lucifer yellow CH attached to the sialic acid residues, were added to the culture medium, the cells incorporated the derivatives and their surfaces became highly fluorescent. When the cells were stained with anti-fibronectin antibodies and a fluorescent second antibody, fibrillar strands of fibronectin were observed to be attached to the cell surface, with partial coincidence of the patterns of direct ganglioside fluorescence and indirect fibronectin immunofluorescence at the cell surface. When the cells were exposed to bacterial neuraminidase during the time of ganglioside insertion, similar patterns of fluorescence were observed. Because the fluorescent gangliosides are resistant to the enzyme, these results suggest that neuraminidase-sensitive endogenous glycoconjugates were not involved in the ganglioside-mediated retention and organization of endogenous fibronectin. After cells were exposed to exogenous chicken fibronectin, most of the fibronectin was attached to the substratum and only a few fibrils were attached to the cells. When exogenous gangliosides were included in the incubation, there was a striking increase in cell-associated exogenous fibronectin, which was highly organized into a fibrillar network. Conversely, cells incubated for 18 h with exogenous unmodified gangliosides exhibited a highly organized network of endogenously derived fibronectin. Upon further incubation of the cells for 2 h with fluorescent gangliosides, there was considerable co-distribution of the fluorescent gangliosides with the fibronectin network as revealed by immunofluorescence. Our results support the concept that gangliosides can mediate the attachment of fibronectin to the cell surface and its organization into a fibrillar

  3. Gangliosides in the Nervous System: Biosynthesis and Degradation

    NASA Astrophysics Data System (ADS)

    Yu, Robert K.; Ariga, Toshio; Yanagisawa, Makoto; Zeng, Guichao

    Gangliosides, abundant in the nervous system, are known to play crucial modulatory roles in cellular recognition, interaction, adhesion, and signal transduction, particularly during early developmental stages. The expression of gangliosides in the nervous system is developmentally regulated and is closely related to the differentiation state of the cell. Ganglioside biosynthesis occurs in intracellular organelles, from which gangliosides are transported to the plasma membrane. During brain development, the ganglioside composition of the nervous system undergoes remarkable changes and is strictly regulated by the activities of glycosyltransferases, which can occur at different levels of control, including glycosyltransferase gene transcription and posttranslational modification. Genes for glycosyltransferase involved in ganglioside biosynthesis have been cloned and classified into families of glycosyltransferases based on their amino acid sequence similarities. The donor and acceptor substrate specificities are determined by enzymatic analysis of the glycosyltransferase gene products. Cell-type specific regulation of these genes has also been studied. Gangliosides are degraded by lysosomal exoglycosidases. The action of these enzymes occurs frequently in cooperation with activator proteins. Several human diseases are caused by defects of degradative enzymes, resulting in massive accumulation of certain glycolipids, including gangliosides in the lysosomal compartment and other organelles in the brain and visceral organs. Some of the representative lysosomal storage diseases (LSDs) caused by the accumulation of lipids in late endosomes and lysosomes will be discussed.

  4. Autoantibodies against ganglioside GM3 are associated with narcolepsy-cataplexy developing after Pandemrix vaccination against 2009 pandemic H1N1 type influenza virus.

    PubMed

    Saariaho, Anna-Helena; Vuorela, Arja; Freitag, Tobias L; Pizza, Fabio; Plazzi, Giuseppe; Partinen, Markku; Vaarala, Outi; Meri, Seppo

    2015-09-01

    Following the mass vaccinations against pandemic influenza A/H1N1 virus in 2009, a sudden increase in juvenile onset narcolepsy with cataplexy (NC) was detected in several European countries where AS03-adjuvanted Pandemrix vaccine had been used. NC is a chronic neurological disorder characterized by excessive daytime sleepiness and cataplexy. In human NC, the hypocretin-producing neurons in the hypothalamus or the hypocretin signaling pathway are destroyed by an autoimmune reaction. Both genetic (e.g. HLA-DQB1*0602) and environmental risk factors (e.g. Pandemrix) contribute to the disease development, but the underlying and the mediating immunological mechanisms are largely unknown. Influenza virus hemagglutinin is known to bind gangliosides, which serve as host cell virus receptors. Anti-ganglioside antibodies have previously been linked to various neurological disorders, like the Guillain-Barré syndrome which may develop after infection or vaccination. Because of these links we screened sera of NC patients and controls for IgG anti-ganglioside antibodies against 11 human brain gangliosides (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b) and a sulfatide by using a line blot assay. Samples from 173 children and adolescents were analyzed: 48 with Pandemrix-associated NC, 20 with NC without Pandemrix association, 57 Pandemrix-vaccinated and 48 unvaccinated healthy children. We found that patients with Pandemrix-associated NC had more frequently (14.6%) anti-GM3 antibodies than vaccinated healthy controls (3.5%) (P = 0.047). Anti-GM3 antibodies were significantly associated with HLA-DQB1*0602 (P = 0.016) both in vaccinated NC patients and controls. In general, anti-ganglioside antibodies were more frequent in vaccinated (18.1%) than in unvaccinated (7.3%) individuals (P = 0.035). Our data suggest that autoimmunity against GM3 is a feature of Pandemrix-associated NC and that autoantibodies against gangliosides were induced by Pandemrix vaccination

  5. The sites of Gd3 + in the luminescent matrix La1 - xGdxMgAl11O19: Single crystal structure determination and site-selective excitation of Gd3 +

    NASA Astrophysics Data System (ADS)

    Salem, Y.; Linares, C.; Jacquier, B.; Saine, M. C.; Gasperin, M.; Lejus, A. M.; Vivien, D.

    1990-11-01

    Single crystals of La1-xGdxMgAl11O19 for x=0.02 to 1 have been grown from the melt by the Verneuil (flame fusion) method. The localization of Gd3+ ions in the matrix has been obtained using x-ray diffraction and Gd3+ fluorescence techniques giving the average and the local structure of the material. The resolution of the crystal structure, of La0.4Gd0.6MgAl11O19 homolog, indicates that this compound is of the distorted magnetoplumbite (MP) type (hexagonal P63/ mmc). Lanthanide ions lie in the mirror plane in two kinds of sites: the (2d) regular MP one (D3h symmetry) occupied by La3+ ions, the distorted (12j) one (Cs symmetry) partially filled up and containing only Gd3+. Some oxygen ions of the Ln coordination polyhedron may be missing leading to a lowering of the true symmetry of the sites. Site selective excitation of the fluorescence of Gd3+ and emission spectra have been carried out on crystals with different x values. It indicates that Gd3+ ions are distributed mainly among two sites, A and B. Crystal field analysis of the splitting of the 6P terms of Gd3+ determined on the excitation spectra show that site A is close to the ideal D3h symmetry while site B is a strongly distorted site. This leads to the identification A=(2d), B=(12j). The occupancy is larger for site B than for site A in agreement with the refinement of the structure. Selective laser excitation into the A site induces emission of the B sites as a result of energy transfer which is demonstrated by the fluorescence decay. No evidence of energy migration is found for gadolinium content up to 100%. Fluorescence spectroscopy and crystal structure determination appear complementary to obtain a detailed description of the sites of Gd3+ in La1-xGdxMgAl11O19.

  6. Nanometer Scale Distance Measurements for Biological Systems using Gd^3+-based Spin Probes at High Magnetic Fields

    NASA Astrophysics Data System (ADS)

    Edwards, Devin; Goldfarb, Daniella; Han, Songi; Sherwin, Mark

    2012-02-01

    Determination of nanometer-scale distances is critical for understanding structure and dynamics of proteins. Electron Paramagnetic Resonance (EPR), primarily below 1 T, is used to complement other structural techniques by quantifying sparse distances up to 8 nm in biomolecules labeled with nitroxide-based radicals. EPR becomes more powerful with increasing magnetic fields and frequencies. At 95 GHz (3.5 T), Gd^3+ ions have shown clear advantages over nitroxide probes (Potapov, JACS 2010). We show that these advantages are even more dramatic at 240 GHz (8.5 T). The width of Gd^3+'s central EPR transition narrows with increasing average distance between Gd^3+ ions out to distances as long as 5 nm. This doubles the distances accessible with nitroxides in continuous wave measurements, which can be carried out above the 200K protein-glass transition and with broad distance distributions. Temperature-dependent measurements of the phase memory times at 8.5 T and low temperatures show distance dependence out to 10 nm. Measurements of Gd^3+ labeled Proteorhodopsin confirm that phase memory times remain long enough to observe distance dependence in a spin-labeled protein. This work is supported by the National Science Foundation and the Binational Science Foundation.

  7. Green-Emitting Gd3Ga5O12: Tb3+ Nanoparticles Phosphor: Synthesis, Structure, and Luminescence

    NASA Astrophysics Data System (ADS)

    Luchechko, A.; Kostyk, L.; Varvarenko, S.; Tsvetkova, O.; Kravets, O.

    2017-04-01

    Nano- and microceramics of Gd3Ga5O12 garnet doped with 1 mol % Tb3+ ions were synthesized via co-precipitation and high-temperature solid-state reaction methods. X-ray diffraction measurements confirmed the formation of the garnet structure with Ia3d space group in all investigated samples. Atomic force microscopy surface images and grain-size distribution diagrams of Gd3Ga5O12: 1 mol % Tb3+ nanoceramics with 300 and 400 g/mol of polyethylene glycol (PEG) were obtained. The relationship between the content of polyethylene glycol and the particle size of Gd3Ga5O12: Tb3+ phosphors was revealed. An intense broad band ( λ m = 266 nm) related to spin-allowed 4 f 8-4 f 75 d 1 transitions of Tb3+ ions was found in photoluminescence excitation spectra of Gd3Ga5O12: Tb3+ nanocrystalline ceramics with PEG-300 and PEG-400 at 300 K. The broad excitation band caused by spin-forbidden ( λ m = 295 nm) 4 f-5 d transitions in Tb3+ ions was additionally observed in the photoluminescence excitation spectra of Gd3Ga5O12: Tb3+ microceramics. Emission of Tb3+ ions under X-ray and UV excitations is presented by two groups of sharp lines which correspond to 5D3 and 5D4 → 7Fj transitions of Tb3+ ions with the most intense line at 546 nm (5D4 → 7F5). It was established that the increasing of PEG content leads to the decreasing of the X-ray and photoluminescence emission intensities.

  8. Magnetooptics of the luminescent transitions in Tb3+:Gd3Ga5O12

    NASA Astrophysics Data System (ADS)

    Valiev, Uygun V.; Gruber, John B.; Ivanov, Igor'A.; Burdick, Gary W.; Liang, Hongbin; Zhou, Lei; Fu, Dejun; Pelenovich, Oleg V.; Pelenovich, Vasiliy O.; Lin, Zhou

    2015-08-01

    The spectra of the luminescence and magnetic circular polarization of luminescence in terbium-gadolinium gallium garnet Tb3+:Gd3Ga5O12 (Tb3+:GGG) were studied within the visible spectral range at temperatures T = 90 and 300 K in an external magnetic field of 0.45 T. The Zeeman effect in the luminescence "green" band associated with 4f → 4f transition 5D4 → 7F5 of Tb3+:GGG was also studied at T = 90 K in an external field of 0.55 T. Measurement of the Zeeman effect in Tb3+:GGG carried out for some doublet lines of the luminescence band 5D4 → 7F5 at T = 90 K shows that a magnetooptical effect of the intensity change of the emitted light is observed on these lines, in contrast to pure Zeeman splitting of the emission lines measured in the luminescence band 5D4 → 7F6. For the systems we have studied, the maximal value of the magnetooptical effect of the intensity change of the luminescence line at low temperatures has been achieved in paramagnetic garnet Tb0.2Y2.8Al5O12 at comparatively low magnetic fields.

  9. The Growth and Measurement of Single-Crystal Doped GGG (Gd3-xCaxGa5-xZrx012),

    DTIC Science & Technology

    1983-08-10

    HD-Ri.31 875 THE GROWTH AIND MEASUREMENT OF SINGLE-CRYSTAL DOPED GGG i/i ( GD3 -XCRXGR5 XZRXi2)(U) FOREIGN TECHNOLOGY DIY WRIGHT-PATTERSON RFB OH...including several steps of compounding materials, growth, etc. (4) The compounding ratios of raw materials were Gd3 -xCaxGaSxZrx 0 1 2, primarily

  10. Surfactant-free Gd3+-ion-containing carbon nanotube MRI contrast agents for stem cell labeling

    NASA Astrophysics Data System (ADS)

    Gizzatov, Ayrat; Hernández-Rivera, Mayra; Keshishian, Vazrik; Mackeyev, Yuri; Law, Justin J.; Guven, Adem; Sethi, Richa; Qu, Feifei; Muthupillai, Raja; Cabreira-Hansen, Maria Da Graça; Willerson, James T.; Perin, Emerson C.; Ma, Qing; Bryant, Robert G.; Wilson, Lon J.

    2015-07-01

    There is an ever increasing interest in developing new stem cell therapies. However, imaging and tracking stem cells in vivo after transplantation remains a serious challenge. In this work, we report new, functionalized and high-performance Gd3+-ion-containing ultra-short carbon nanotube (US-tube) MRI contrast agent (CA) materials which are highly-water-dispersible (ca. 35 mg ml-1) without the need of a surfactant. The new materials have extremely high T1-weighted relaxivities of 90 (mM s)-1 per Gd3+ ion at 1.5 T at room temperature and have been used to safely label porcine bone-marrow-derived mesenchymal stem cells for MR imaging. The labeled cells display excellent image contrast in phantom imaging experiments, and TEM images of the labeled cells, in general, reveal small clusters of the CA material located within the cytoplasm with 109 Gd3+ ions per cell.There is an ever increasing interest in developing new stem cell therapies. However, imaging and tracking stem cells in vivo after transplantation remains a serious challenge. In this work, we report new, functionalized and high-performance Gd3+-ion-containing ultra-short carbon nanotube (US-tube) MRI contrast agent (CA) materials which are highly-water-dispersible (ca. 35 mg ml-1) without the need of a surfactant. The new materials have extremely high T1-weighted relaxivities of 90 (mM s)-1 per Gd3+ ion at 1.5 T at room temperature and have been used to safely label porcine bone-marrow-derived mesenchymal stem cells for MR imaging. The labeled cells display excellent image contrast in phantom imaging experiments, and TEM images of the labeled cells, in general, reveal small clusters of the CA material located within the cytoplasm with 109 Gd3+ ions per cell. Electronic supplementary information (ESI) available: NMRD profiles, the Fourier transforms of the EXAFS data, EXAFS curve fitting data, cell viability data. See DOI: 10.1039/c5nr02078f

  11. Influence of Li+ charge compensator ion on the energy transfer from Pr3 + to Gd3 + ions in Ca9Mg(PO4)6F2:Gd3 +, Pr3 +, Li+ phosphor

    NASA Astrophysics Data System (ADS)

    Tamboli, Sumedha; Dhoble, S. J.

    2017-09-01

    Phototherapy is a renowned treatment for curing skin diseases since ancient times. Phototherapeutic treatment for psoriasis and many other diseases require narrow band ultra violet-B (NB-UVB) light with peak intensity at 313 nm to be exposed to the affected part of body. In this paper, we report combustion synthesis of NB-UVB - 313 nm emitting Ca9Mg(PO4)6F2 phosphors doped with Gd3 +, Pr3 + and Li+ ions. The phase formation was confirmed by obtaining X-ray diffraction (XRD) pattern and morphology was studied with the Scanning electron microscopy (SEM) images. Photoluminescence (PL) emission spectra show intense narrow band emission at 313 nm under 274 nm excitation wavelengths. Emission intensity was enhanced when Ca9Mg(PO4)6F2 compound is co-doped with Pr3 + ions. Excitation spectra of Ca9Mg(PO4)6F2:Gd3 +, Pr3 + doped samples shows broad excitation in ultra violet C (UVC) region. Diffuse reflectance spectra (DRS), obtained by UV-visible spectrophotometer, measures the absorption properties of the material. By applying Kubelka Munk function on the diffuse reflectance spectra, band gap of the material is determined. PL decay curves were examined which indicates efficient energy transfer between Pr3 + and Gd3 + ions. Charge compensation effect was also studied by co-doping Li+ ion in host. Emission intensity was found to increase with the addition of charge compensator. The prepared phosphor has potential to convert UVC light into NB-UVB. The luminescence intensity of Gd3 + shows remarkable increase when it is sensitized with Pr3 +, and an addition of charge compensator in the form of Li+, show even better results. This phosphor surely has the potential to be used as phototherapy lamp phosphor.

  12. Electrical and electromechanical studies in ferroelectric Gd3+ modified lead potassium niobate ceramics

    NASA Astrophysics Data System (ADS)

    Sambasiva Rao, K.; Krishna, P. Murali; Dasari, Madhava P.; Lee, J. H.

    2011-08-01

    The change in dielectric constant relaxation time over temperature (35-590 °C) and frequency (45 Hz-5 MHz) in ceramics of Pb0.77K0.115Gd0.115Nb2O6 (PKGN, Tc = 340 °c) has been studied. Powder X-ray diffraction revealed the single-phase formation with orthorhombic crystal structure. The P-E hysteresis loop parameters are Ps = 21.77 μC/cm2, Pr = 17.09 μC/cm2, Ec = 11.86 kV/cm; the piezoelectric constants, Kp = 31.7%, Kt = 47%, d33 = 115 × 10-12 C/N, d31 = -41 × 10-12 C/N, are determined in the material and some transducer applications are discussed. Cole-Cole (Zll vs. Zl) plots showed a non-Debye type relaxation. Conductivity obeyed Jonscher's universal power law, σ = σ0 + Aωn. The theoretical values of ɛl and σ are computed using the parameters `A(T)' and `n(T)' (0 < n < 1) and are well fitted with the experimental data. The hopping ion frequency (ωp) and charge carrier concentration (Kl) have been analyzed using Almond-West formalism. The dielectric relaxation processes are associated with localized oxygen vacancies conduction at high frequency region. A long-range conductivity by Gd3+ ions is found to be predominant at low frequency region. The activation energies from impedance and modulus formalisms revealed the ionic type conduction in PKGN.

  13. Gd(3+)-loaded polyion complex for pH depiction with magnetic resonance imaging.

    PubMed

    Mikawa, M; Miwa, N; Bräutigam, M; Akaike, T; Maruyama, A

    2000-03-05

    In clinical diagnosis, gadolinium (Gd) ion/low molecular weight chelater complexes have been used as MRI contrast agents that disperse throughout a particular tissue and cause a brighter appearance in MRI. In order to provide a novel imaging concept for MRI, a contrast agent in which the T(1)-relaxation shortening activity (R(1) relaxivity) changes in response to the pH differences was studied. We prepared a polyion complex (PIC) consisting of a polyanionic Gd-chelater, poly(diethylenetriamine-N,N,N',N", N"-pentaaceto, DTPA) (1,3-propanediamide) (denoted as 1a) loaded with Gd ions at a [Gd]/[DTPA unit] ratio of 0.2 (denoted as 1b), and a polycation, poly[2-(diethylamino)ethyl methacrylate] (denoted as 2). The stoichiometric (based on ionic groups) mixture of 1b and 2 formed complex coacervates from pH 5 to pH 8. The R(1) relaxivity of Gd(3+) in the complex was considerably influenced by the pH, and the relative signal intensity changed from 4 at pH 7.2 to 11 at pH 5.0, as determined by an MRI phantom study. The pH responsivity of the complex solution varied with the composition of the PIC (i.e., the mixing ratio of 1b and 2), allowing us to modulate the pH sensibility. The ionic charge balance and swelling of PIC seemingly were related to the pH-dependent R(1) relaxivity change. It is expected that the PIC-based MRI contrast agent may provide a novel category of MRI methods and be useful in improving the detectability of an MRI-based diagnosis. Copyright 2000 John Wiley & Sons, Inc.

  14. Recent progress in advanced optical materials based on gadolinium aluminate garnet (Gd3Al5O12).

    PubMed

    Li, Ji-Guang; Sakka, Yoshio

    2015-02-01

    This review article summarizes the recent achievements in stabilization of the metastable lattice of gadolinium aluminate garnet (Gd3Al5O12, GAG) and the related developments of advanced optical materials, including down-conversion phosphors, up-conversion phosphors, transparent ceramics, and single crystals. Whenever possible, the materials are compared with their better known YAG and LuAG counterparts to demonstrate the merits of the GAG host. It is shown that novel emission features and significantly improved luminescence can be attained for a number of phosphor systems with the more covalent GAG lattice and the efficient energy transfer from Gd(3+) to the activator. Ce(3+) doped GAG-based single crystals and transparent ceramics are also shown to simultaneously possess the advantages of high theoretical density, fast scintillation decay, and high light yields, and hold great potential as scintillators for a wide range of applications. The unresolved issues are also pointed out.

  15. Recent progress in advanced optical materials based on gadolinium aluminate garnet (Gd3Al5O12)

    PubMed Central

    Li, Ji-Guang; Sakka, Yoshio

    2015-01-01

    This review article summarizes the recent achievements in stabilization of the metastable lattice of gadolinium aluminate garnet (Gd3Al5O12, GAG) and the related developments of advanced optical materials, including down-conversion phosphors, up-conversion phosphors, transparent ceramics, and single crystals. Whenever possible, the materials are compared with their better known YAG and LuAG counterparts to demonstrate the merits of the GAG host. It is shown that novel emission features and significantly improved luminescence can be attained for a number of phosphor systems with the more covalent GAG lattice and the efficient energy transfer from Gd3+ to the activator. Ce3+ doped GAG-based single crystals and transparent ceramics are also shown to simultaneously possess the advantages of high theoretical density, fast scintillation decay, and high light yields, and hold great potential as scintillators for a wide range of applications. The unresolved issues are also pointed out. PMID:27877750

  16. Controlling the Two-Photon-Induced Photon Cascade Emission in a Gd3+/Tb3+-Codoped Glass for Multicolor Display

    PubMed Central

    Yuan, Mao-Hui; Fan, Hai-Hua; Li, Hui; Lan, Sheng; Tie, Shao-Long; Yang, Zhong-Min

    2016-01-01

    We reported the first observation of the two-photon-induced quantum cutting phenomenon in a Gd3+/Tb3+-codoped glass in which two photons at ~400 nm are simultaneously absorbed, leading to the cascade emission of three photons in the visible spectral region. The two-photon absorption induced by femtosecond laser pulses allows the excitation of the energy states in Gd3+ which are inactive for single-photon excitation and enables the observation of many new electric transitions which are invisible in the single-photon-induced luminescence. The competition between the two-photon-induced photon cascade emission and the single-photon-induced emission was manipulated to control the luminescence color of the glass. We demonstrated the change of the luminescence color from red to yellow and eventually to green by varying either the excitation wavelength or the excitation power density. PMID:26899189

  17. Controlling the Two-Photon-Induced Photon Cascade Emission in a Gd(3+)/Tb(3+)-Codoped Glass for Multicolor Display.

    PubMed

    Yuan, Mao-Hui; Fan, Hai-Hua; Li, Hui; Lan, Sheng; Tie, Shao-Long; Yang, Zhong-Min

    2016-02-22

    We reported the first observation of the two-photon-induced quantum cutting phenomenon in a Gd(3+)/Tb(3+)-codoped glass in which two photons at ~400 nm are simultaneously absorbed, leading to the cascade emission of three photons in the visible spectral region. The two-photon absorption induced by femtosecond laser pulses allows the excitation of the energy states in Gd(3+) which are inactive for single-photon excitation and enables the observation of many new electric transitions which are invisible in the single-photon-induced luminescence. The competition between the two-photon-induced photon cascade emission and the single-photon-induced emission was manipulated to control the luminescence color of the glass. We demonstrated the change of the luminescence color from red to yellow and eventually to green by varying either the excitation wavelength or the excitation power density.

  18. Linear and nonlinear optical properties of Gd3+ doped zinc borotellurite glasses for all-optical switching applications

    NASA Astrophysics Data System (ADS)

    Eevon, C.; Halimah, M. K.; Zakaria, A.; Azurahanim, C. A. C.; Azlan, M. N.; Faznny, M. F.

    In this work, linear and nonlinear optical parameters of zinc borotellurite glasses doped with Gd3+ have been studied for all-optical switching applications. A series of gadolinium zinc borotellurite glasses were synthesized by using conventional melt quenching technique. Optical absorption spectra were recorded by UV-vis spectroscopy. From the optical absorption spectra, the cut-off wavelength, optical band gap, Urbach energy and refractive index have been determined and are related to the structural changes in the glass systems. The nonlinear optical properties of Gd3+ doped glasses are investigated by using Z-scan technique. The values of nonlinear refractive index and absorption coefficient with closed and opened apertures of the Z-scan, respectively, were determined for proper utilization in nonlinear optical devices.

  19. Recent progress in advanced optical materials based on gadolinium aluminate garnet (Gd3Al5O12)

    NASA Astrophysics Data System (ADS)

    Li, Ji-Guang; Sakka, Yoshio

    2015-02-01

    This review article summarizes the recent achievements in stabilization of the metastable lattice of gadolinium aluminate garnet (Gd3Al5O12, GAG) and the related developments of advanced optical materials, including down-conversion phosphors, up-conversion phosphors, transparent ceramics, and single crystals. Whenever possible, the materials are compared with their better known YAG and LuAG counterparts to demonstrate the merits of the GAG host. It is shown that novel emission features and significantly improved luminescence can be attained for a number of phosphor systems with the more covalent GAG lattice and the efficient energy transfer from Gd3+ to the activator. Ce3+ doped GAG-based single crystals and transparent ceramics are also shown to simultaneously possess the advantages of high theoretical density, fast scintillation decay, and high light yields, and hold great potential as scintillators for a wide range of applications. The unresolved issues are also pointed out.

  20. Effect of Gd3+- Cr3+ ion substitution on the structural, electrical and magnetic properties of Ni - Zn ferrite nanoparticles

    NASA Astrophysics Data System (ADS)

    Anupama, M. K.; Rudraswamy, B.

    2016-09-01

    Gd3+ doped nickel zinc nanoceramics with general formula Ni0.4Zn0.6Cr0.5GdxFe1.5 - xO4 (where x=0.00, 0.02, 0.04, 0.06) were synthesized by solution combustion method using oxylyldehydrazine as a fuel. The obtained powder was sintered at 1000°C for 2h. The detailed structural, electrical and magnetic studies were carried out through X-ray diffractometer (XRD), Fourier transform infrared spectroscopy (FTIR), impedance spectroscopy and vibrating sample magnetometer (VSM). The XRD pattern of as prepared sample confirms the formation of single phase with cubic spinel structure. The average crystallite size was found to be 34 to 19 nm and decreases with increasing Gd3+ ion concentration. The IR spectra exhibited two expected absorption bands between 600 to 300 cm-1 corresponding to the stretching vibrations of tetrahedral (A) and octahedral (B) metal oxygen vibrations. The variation of room temperature real (ε') and imaginary (ε") part of dielectric permittivity as a function of frequency and composition have been studied in the frequency range from 40Hz to 10MHz. The real and imaginary dielectric permittivity decreases with increase in frequency as well as Gd3+ concentration, which is normal behaviour of ferrite material and results have been explained on the basis of Maxwell - Wagner's two layer model. The VSM results showed that the Gd3+ concentration had significant impact on the saturation magnetization and coercivity, x = 0.02 shows the highest value of dielectric constant and saturation magnetization, thus the material is becoming low loss dielectric and highly resistive and soft magnetic material due to Gd-Cr doping.

  1. Li3Gd3Te2O12:Eu3+- an intense red phosphor for solid state lighting applications

    NASA Astrophysics Data System (ADS)

    Tiwari, Hansnath; Asiri Naidu, S.; Varadaraju, U. V.

    2017-02-01

    Li3Gd3-3xEu3xTe2O12 (x=0.05-1.0) phases with garnet structure were synthesized by high temperature solid state reaction and the photoluminescence properties were investigated. The appearance of bands due to intra 4 f transitions of Gd3+ in the excitation spectra recorded by monitoring the 612 nm emission line of the activator indicates Gd3+→Eu3+ energy transfer in this host lattice. Under 395 nm excitation, the electric dipole transition is predominant in the emission spectrum of Eu3+ and is in agreement with the C2 point group (noncentrosymmetric) of the EuO8 polyhedron. The critical concentration of the Eu3+ activator in this series was found to be 0.6 (x=0.2) above which, concentration quenching occurs. The emission intensity of the phosphor composition, Li3Gd2.4Eu0.6Te2O12 is 4 times that of the commercial sample of Y2O3:Eu3+ phosphor.

  2. Investigations of the spin Hamiltonian parameters and defect structure for the rhombic Gd3+ center in calcium oxide

    NASA Astrophysics Data System (ADS)

    Wu, S. Y.; Dongo, H. N.; Lin, J. Z.; Fu, Q.

    2006-09-01

    The spin Hamiltonian (SH) parameters (zero-field splittings, b(2)(0), b(2)(2), b(4)(0), b(4)(2), b(4)(4), b(6)(0) and b(6)(6)) and the defect structure for the rhombic Gd3+ center in CaO are theoretically investigated by the superposition model. Meanwhile, the g-factor is also quantitatively studied from the approximation formula on the basis of an admixture of the ground S-8(7/2) and the excited L-6(7/2) (L = P, D, F, G) states via the spin-orbit coupling interactions. The defect structure of this center can be described by the impurity Gd3+ occupying the host octahedral Ca2+ site, associated with one nearest neighbouring cation vacancy V-Ca in the [110] direction. On the basis of these studies, the impurity Gd3+ is found to shift towards the V-Ca along the [110] axis by about 0.582 angstrom, whereas the oxygen ligands closest to the V-Ca suffer a displacement towards the latter by about 0.211 angstrom. The calculated SH parameters based on the earlier analyses show reasonable agreement with the observed values.

  3. Spin transition in Gd3N@C80, detected by low-temperature on-chip SQUID technique

    NASA Astrophysics Data System (ADS)

    Chen, L.; Carpenter, E. E.; Hellberg, C. S.; Dorn, H. C.; Shultz, M.; Wernsdorfer, W.; Chiorescu, I.

    2011-04-01

    We present a magnetic study of the Gd3N@C80 molecule, consisting of a Gd-trimer via a nitrogen atom, encapsulated in a C80 cage. This molecular system can be an efficient contrast agent for magnetic resonance imaging (MRI) applications. We used a low-temperature technique able to detect small magnetic signals by placing the sample in the vicinity of an on-chip SQUID. The technique implemented at the National High Magnetic Field Laboratory has the particularity of being able to operate in high magnetic fields of up to 7 T. The Gd3N@C80 shows a paramagnetic behavior and we find a spin transition of the Gd3N structure at 1.2 K. We perform quantum mechanical simulations, which indicate that one of the Gd ions changes from a 8S7/2 state (L = 0, S = 7/2) to a 7F6 state (L = S = 3, J = 6), likely due to a charge transfer between the C80 cage and the ion.

  4. The effects of Gd3+ doping on the physical structure and photocatalytic performance of Bi2MoO6 nanoplate crystals

    NASA Astrophysics Data System (ADS)

    Yu, Changlin; Wu, Zhen; Liu, Renyue; He, Hongbo; Fan, Wenhong; Xue, Shuangshuang

    2016-06-01

    Gd3+ doped Bi2MoO6 nanoplate crystals were fabricated by solvothermal combined calcination method. The effects of Gd3+ doping with different concentrations on the texture, crystal and optical properties of Bi2MoO6 were investigated by N2 physical adsorption, X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR) and ultraviolet-visible diffuse reflection spectrum (UV-vis DRS), photoluminescence (PL) spectroscopy, and X-ray photoelectron spectroscopy (XPS). Under simulated solar light irradiation, the influences of Gd3+doping on photocatalytic activity of Bi2MoO6 were evaluated by photocatalytic degradation of Rhodamine B. The characterization results showed that with Gd3+ doping, a contraction of lattice and a decrease in crystallite size occurred. Meanwhile, an increase in surface area over Gd3+ doped Bi2MoO6 was observed. Moreover, Gd3+ doping could obviously enhance the visible light harvesting of Bi2MoO6 and promoted the separation of photogenerated electrons and holes. With optimum Gd3+(6 wt%) doping, Gd/Bi2MoO6 exhibited the best activity and stability in degradation of Rhodamine B.

  5. Depletion of gangliosides enhances cartilage degradation in mice.

    PubMed

    Sasazawa, F; Onodera, T; Yamashita, T; Seito, N; Tsukuda, Y; Fujitani, N; Shinohara, Y; Iwasaki, N

    2014-02-01

    Glycosphingolipids (GSLs) are ubiquitous membrane components that play a functional role in maintaining chondrocyte homeostasis. We investigated the potential role of gangliosides, one of the major components of GSLs, in osteoarthritis (OA) pathogenesis. Both age-associated and instability-induced OA models were generated using GM3 synthase knockout (GM3S(-/-)) mice. A cartilage degradation model and transiently GM3S-transfected chondrocytes were analyzed to evaluate the function of gangliosides in OA development. The amount of each series of GSLs in chondrocytes after IL-1α stimulation was profiled using mass spectrometry (MS). OA changes in GM3S(-/-) mice were dramatically enhanced with aging compared to those in wild-type (WT) mice. GM3S(-/-) mice showed more severe instability-induced pathologic OA in vivo. Ganglioside deficiency also led to the induction of matrix metalloproteinase (MMP)-13 and ADAMTS-5 secretion and chondrocyte apoptosis in vitro. In contrast, transient GM3S transfection of chondrocytes suppressed MMP-13 and ADAMTS-5 expression after interleukin (IL)-1α stimulation. GSL profiling revealed the presence of abundant gangliosides in chondrocytes after IL-1α stimulation. Gangliosides play a critical role in OA pathogenesis by regulating the expression of MMP-13 and ADAMTS-5 and chondrocyte apoptosis. Based on the obtained results, we propose that gangliosides are potential target molecules for the development of novel OA treatments. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  6. Biosynthesis and transport of gangliosides in peripheral nerve

    SciTech Connect

    Yates, A.J.; Tipnis, U.R.; Hofteig, J.H.; Warner, J.K.

    1984-01-01

    Radiolabelled glucosamine was injected into L-7 dorsal root ganglion (DRG) of rabbits. At several different times after injection DRG, lumbosacral trunks (LST) and sciatic nerves (SN) were removed and gangliosides extracted. Two and 3 weeks after injection the amounts of radioactivity in the ganglioside fractions of LST and SN were significantly higher than at days 1 and 2. The TCA soluble radioactivity decreased dramatically over the same time period. Colchicine prevented the appearance of radiolabelled lipid in LST and SN. From these experiments the authors conclude that some ganglioside is synthesized in the neuronal cell bodies of DRG and transported in the axons of the sciatic nerve. In another experiment the sciatic nerve was transected and ends separated to prevent regeneration. There was no difference in the amount of radiolabelled ganglioside that was isolated from DRG or LST of transected nerves compared with control nerves. The behavior of several potential acid soluble contaminants was studied in several steps used to isolate gangliosides. Of those studied only CMP-NeuAc could cause significant contamination of the final ganglioside preparation.

  7. Mode of interaction of ganglioside Langmuir monolayer originated from echinoderms: three binary systems of ganglioside/DPPC, ganglioside/DMPE, and ganglioside/cholesterol.

    PubMed

    Hoda, Kazuki; Ikeda, Yuriko; Kawasaki, Hideya; Yamada, Koji; Higuchi, Ryuichi; Shibata, Osamu

    2006-09-01

    The surface pressure (pi)-area (A), the surface potential (DeltaV)-A, and the dipole moment (mu( perpendicular))-A isotherms were obtained for monolayers made from a ganglioside originated from echinoderms [Diadema setosum ganglioside (DSG-1)], dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylethanolamine (DMPE), cholesterol (Ch), and their combinations. Monolayers spread on several different substrates were investigated at the air/water interface by the Wilhelmy method, ionizing electrode method, fluorescence microscopy (FM) and atomic force microscopy (AFM). Surface potentials (DeltaV) of pure components were analyzed using the three-layer model proposed by Demchak and Fort [R.J. Demchak, T. Fort, J. Colloid Interface Sci. 46 (1974) 191-202]. The new finding was that DSG-1 was stable and showed a liquid-expanded film and that its monolayer behavior of DeltaV was sensitive for the change of the NaCl concentration in the subphase. Moreover, the miscibility of DSG-1 and three major lipids in the two-component monolayers was examined by plotting the variation of the molecular area and the surface potential as a function of the DSG-1 molar fraction (X(DSG-1)), using the additivity rule. From the A-X(DSG-1) and DeltaV(m)-X(DSG-1) plots, partial molecular surface area (PMA) and apparent partial molecular surface potential (APSP) were determined at the discrete surface pressure. The PMA and APSP with the mole fraction were extensively discussed for the miscible system. The miscibility was also investigated from the two-dimensional phase diagrams. Furthermore, a regular surface mixture, for which the Joos equation was used for the analysis of the collapse pressure of two-component monolayers, allowed calculation of the interaction parameter (xi) and the interaction energy (-Deltavarepsilon) between them. The observations using fluorescence microscopy and AFM image also provide us the miscibility in the monolayer state.

  8. Guillain-Barré Syndrome-Related Campylobacter jejuni in Bangladesh: Ganglioside Mimicry and Cross-Reactive Antibodies

    PubMed Central

    Islam, Zhahirul; Gilbert, Michel; Mohammad, Quazi D.; Klaij, Kevin; Li, Jianjun; van Rijs, Wouter; Tio-Gillen, Anne P.; Talukder, Kaisar A.; Willison, Hugh J.; van Belkum, Alex; Endtz, Hubert P.; Jacobs, Bart C.

    2012-01-01

    Background Campylobacter jejuni is the predominant antecedent infection in Guillain-Barré syndrome (GBS). Molecular mimicry and cross-reactive immune responses to C. jejuni lipo-oligosaccharides (LOS) precipitate the development of GBS, although this mechanism has not been established in patients from developing countries. We determined the carbohydrate mimicry between C. jejuni LOS and gangliosides, and the cross-reactive antibody response in patients with GBS in Bangladesh. Methodology Sera from 97 GBS patients, and 120 neurological and family controls were tested for antibody reactivity against LOS from C. jejuni isolates from GBS patients in Bangladesh (BD-07, BD-39, BD-10, BD-67 and BD-94) by enzyme-linked immunosorbent assay (ELISA). Cross-reactivity to LOS was determined by ELISA. The LOS outer core structures of C. jejuni strains associated with GBS/MFS were determined by mass spectrometry. Principle Findings IgG antibodies to LOS from C. jejuni BD-07, BD-39, BD-10, and BD-67 IgG antibodies were found in serum from 56%, 58%, 14% and 15% of GBS patients respectively, as compared to very low frequency (<3%) in controls (p<0.001). Monoclonal antibodies specific for GM1 and GD1a reacted strongly with LOS from the C. jejuni strains (BD-07 and BD-39). Mass spectrometry analysis confirmed the presence of GM1 and GD1a carbohydrate mimics in the LOS from C. jejuni BD-07 and BD-39. Both BD-10 and BD-67 express the same LOS outer core, which appears to be a novel structure displaying GA2 and GD3 mimicry. Up to 90–100% of serum reactivity to gangliosides in two patients (DK-07 and DK-39) was inhibited by 50 µg/ml of LOS from the autologous C. jejuni isolates. However, patient DK-07 developed an anti-GD1a immune response while patient DK-39 developed an anti-GM1 immune response. Conclusion Carbohydrate mimicry between C. jejuni LOS and gangliosides, and cross-reactive serum antibody precipitate the majority of GBS cases in Bangladesh. PMID:22952833

  9. Guillain-Barré syndrome-related Campylobacter jejuni in Bangladesh: ganglioside mimicry and cross-reactive antibodies.

    PubMed

    Islam, Zhahirul; Gilbert, Michel; Mohammad, Quazi D; Klaij, Kevin; Li, Jianjun; van Rijs, Wouter; Tio-Gillen, Anne P; Talukder, Kaisar A; Willison, Hugh J; van Belkum, Alex; Endtz, Hubert P; Jacobs, Bart C

    2012-01-01

    Campylobacter jejuni is the predominant antecedent infection in Guillain-Barré syndrome (GBS). Molecular mimicry and cross-reactive immune responses to C. jejuni lipo-oligosaccharides (LOS) precipitate the development of GBS, although this mechanism has not been established in patients from developing countries. We determined the carbohydrate mimicry between C. jejuni LOS and gangliosides, and the cross-reactive antibody response in patients with GBS in Bangladesh. Sera from 97 GBS patients, and 120 neurological and family controls were tested for antibody reactivity against LOS from C. jejuni isolates from GBS patients in Bangladesh (BD-07, BD-39, BD-10, BD-67 and BD-94) by enzyme-linked immunosorbent assay (ELISA). Cross-reactivity to LOS was determined by ELISA. The LOS outer core structures of C. jejuni strains associated with GBS/MFS were determined by mass spectrometry. IgG antibodies to LOS from C. jejuni BD-07, BD-39, BD-10, and BD-67 IgG antibodies were found in serum from 56%, 58%, 14% and 15% of GBS patients respectively, as compared to very low frequency (<3%) in controls (p<0.001). Monoclonal antibodies specific for GM1 and GD1a reacted strongly with LOS from the C. jejuni strains (BD-07 and BD-39). Mass spectrometry analysis confirmed the presence of GM1 and GD1a carbohydrate mimics in the LOS from C. jejuni BD-07 and BD-39. Both BD-10 and BD-67 express the same LOS outer core, which appears to be a novel structure displaying GA2 and GD3 mimicry. Up to 90-100% of serum reactivity to gangliosides in two patients (DK-07 and DK-39) was inhibited by 50 µg/ml of LOS from the autologous C. jejuni isolates. However, patient DK-07 developed an anti-GD1a immune response while patient DK-39 developed an anti-GM1 immune response. Carbohydrate mimicry between C. jejuni LOS and gangliosides, and cross-reactive serum antibody precipitate the majority of GBS cases in Bangladesh.

  10. Investigation of Gd3N@C2n(40≤n≤44) family by Raman and inelastic electron tunneling spectroscopy

    NASA Astrophysics Data System (ADS)

    Burke, Brian G.; Chan, Jack; Williams, Keith A.; Ge, Jiechao; Shu, Chunying; Fu, Wujun; Dorn, Harry C.; Kushmerick, James G.; Puretzky, Alexander A.; Geohegan, David B.

    2010-03-01

    The structure and vibrational spectrum of Gd3N@C80 is studied through Raman and inelastic electron tunneling spectroscopy as well as density-functional theory and universal force field calculations. Hindered rotations, shown by both theory and experiment, indicate the formation of a Gd3N-C80 bond which reduces the ideal icosahedral symmetry of the C80 cage. The vibrational modes involving the movement of the encapsulated species are a fingerprint of the interaction between the fullerene cage and the core complex. We present Raman data for the Gd3N@C2n(40≤n≤44) family as well as Y3N@C80 , Lu3N@C80 , and Y3N@C88 for comparison. Conductance measurements have been performed on Gd3N@C80 and reveal a Kondo effect similar to that observed in C60 .

  11. Gangliosides and gangliosidoses: principles of molecular and metabolic pathogenesis.

    PubMed

    Sandhoff, Konrad; Harzer, Klaus

    2013-06-19

    Gangliosides are the main glycolipids of neuronal plasma membranes. Their surface patterns are generated by coordinated processes, involving biosynthetic pathways of the secretory compartments, catabolic steps of the endolysosomal system, and intracellular trafficking. Inherited defects in ganglioside biosynthesis causing fatal neurodegenerative diseases have been described so far almost exclusively in mouse models, whereas inherited defects in ganglioside catabolism causing various clinical forms of GM1- and GM2-gangliosidoses have long been known. For digestion, gangliosides are endocytosed and reach intra-endosomal vesicles. At the level of late endosomes, they are depleted of membrane-stabilizing lipids like cholesterol and enriched with bis(monoacylglycero)phosphate (BMP). Lysosomal catabolism is catalyzed at acidic pH values by cationic sphingolipid activator proteins (SAPs), presenting lipids to their respective hydrolases, electrostatically attracted to the negatively charged surface of the luminal BMP-rich vesicles. Various inherited defects of ganglioside hydrolases, e.g., of β-galactosidase and β-hexosaminidases, and of GM2-activator protein, cause infantile (with tetraparesis, dementia, blindness) and different protracted clinical forms of GM1- and GM2-gangliosidoses. Mutations yielding proteins with small residual catabolic activities in the lysosome give rise to juvenile and adult clinical forms with a wide range of clinical symptomatology. Apart from patients' differences in their genetic background, clinical heterogeneity may be caused by rather diverse substrate specificities and functions of lysosomal hydrolases, multifunctional properties of SAPs, and the strong regulation of ganglioside catabolism by membrane lipids. Currently, there is no treatment available for neuronal ganglioside storage diseases. Therapeutic approaches in mouse models and patients with juvenile forms of gangliosidoses are discussed.

  12. Gangliosides Block Aggregatibacter Actinomycetemcomitans Leukotoxin (LtxA)-Mediated Hemolysis

    PubMed Central

    Forman, Michael S.; Nishikubo, Jason B.; Han, Rebecca K.; Le, Amy; Balashova, Nataliya V.; Kachlany, Scott C.

    2010-01-01

    Aggregatibacter actinomycetemcomitans is an oral pathogen and etiologic agent of localized aggressive periodontitis. The bacterium is also a cardiovascular pathogen causing infective endocarditis. A. actinomycetemcomitans produces leukotoxin (LtxA), an important virulence factor that targets white blood cells (WBCs) and plays a role in immune evasion during disease. The functional receptor for LtxA on WBCs is leukocyte function antigen-1 (LFA-1), a β-2 integrin that is modified with N-linked carbohydrates. Interaction between toxin and receptor leads to cell death. We recently discovered that LtxA can also lyse red blood cells (RBCs) and hemolysis may be important for pathogenesis of A. actinomycetemcomitans. In this study, we further investigated how LtxA might recognize and lyse RBCs. We found that, in contrast to a related toxin, E. coli α-hemolysin, LtxA does not recognize glycophorin on RBCs. However, gangliosides were able to completely block LtxA-mediated hemolysis. Furthermore, LtxA did not show a preference for any individual ganglioside. LtxA also bound to ganglioside-rich C6 rat glioma cells, but did not kill them. Interaction between LtxA and C6 cells could be blocked by gangliosides with no apparent specificity. Gangliosides were only partially effective at preventing LtxA-mediated cytotoxicity of WBCs, and the effect was only observed when a high ratio of ganglioside:LtxA was used over a short incubation period. Based on the results presented here, we suggest that because of the similarity between N-linked sugars on LFA-1 and the structures of gangliosides, LtxA may have acquired the ability to lyse RBCs. PMID:22069577

  13. [Luminescence properties of Pr(3+) and energy transfer characteristics of Pr(3+)-->Gd(3+) in CaSiO3].

    PubMed

    Chu, Ben-li; Liu, Xing-ren; Wang, Xiao-jun; Zhang, Jia-hua; Jiang, Xue-yin

    2002-08-01

    The excitation spectrum and the emission spectrum of Pr3+ in CaSiO3 under the room temperature were studied. The emission spectrum was constituted of three emission bands, corresponding to the emissions of the lowest 4f5d states to the 3H4, 3H6, 1G4 of the 4f2 states. The emission of the 3P0 and 1D2 were not observed. The concentration quenching of Pr3+ was due to the radiative and nonradiative energy transfer. There was energy transfer from Pr3+ to Gd3+, with the transfer rate of 10% of the Pr3+ emission rate.

  14. Simultaneous dual-wavelength laser operation at 937 and 1062 nm in Nd3+:Gd3Ga5O12

    NASA Astrophysics Data System (ADS)

    Gao, F.; Sun, G. C.; Li, Y. D.; Dong, Y.; Li, S. T.

    2013-08-01

    Diode-end-pumped continuous-wave (cw) simultaneous dual-wavelength laser operation at 937 and 1062 nm in a single Nd3+:Gd3Ga5O12 (Nd:GGG) crystal was demonstrated. A total output power of 1.12 W at the two fundamental wavelengths was achieved at incident pump power of 17.6 W. The optical-to-optical conversion was up to 6.4% with respect to the incident pump power. To the best of our knowledge, this is first work on cw simultaneous dual-wavelength operation at 937 and 1062 nm in Nd:GGG crystal.

  15. Preparation and morphology, magnetic properties of yttrium iron garnet nanodot arrays on Gd3Ga5O12 substrate

    NASA Astrophysics Data System (ADS)

    Xu, Zhiwang; Zheng, Hui; Han, Mangui

    2017-07-01

    In this work, yttrium iron garnet nanodot array has been deposited on Gd3Ga5O12 substrate by pulsed laser deposition through an ultrathin alumina mask. The morphology and magnetic properties of YIG nanodot array have been investigated. Scanning electron microscopy displays the prepared nanodot array has a sharp distribution in diameter centered at 330 nm with standard deviation of 20 nm. X-ray diffraction θ-2θ and pole figure analysis show the yttrium iron garnet nanodot array has oriented growth. Moreover, typical hysteresis loops and ferromagnetic resonance spectra display larger coercivity and multi-resonance peaks which are ascribed to this unique structure.

  16. Combustion synthesis of SrAl4O7:Eu2+, Dy3+, Gd3+ long lasting phosphor

    NASA Astrophysics Data System (ADS)

    Yerpude, A. N.; Dhoble, S. J.

    2015-02-01

    Long afterglow strontium aluminates SrAl4O7:Eu2+,Dy3+,Gd3+ phosphor was prepared by combustion method. The X-ray diffraction (XRD), Scanning electron microscope (SEM) and photoluminescence (PL) spectrum as well as the luminescence decay were used to characterize the long lasting phosphor. The emission spectrum of the phosphor shows broadened band at 495 nm assigned to the 4f65d→4f7(8S7/2) transition of Eu2+. The present phosphor shows green persistent luminescence after removal of the UV light.

  17. Multi-system disorders of glycosphingolipid and ganglioside metabolism

    PubMed Central

    Xu, You-Hai; Barnes, Sonya; Sun, Ying; Grabowski, Gregory A.

    2010-01-01

    Glycosphingolipids (GSLs) and gangliosides are a group of bioactive glycolipids that include cerebrosides, globosides, and gangliosides. These lipids play major roles in signal transduction, cell adhesion, modulating growth factor/hormone receptor, antigen recognition, and protein trafficking. Specific genetic defects in lysosomal hydrolases disrupt normal GSL and ganglioside metabolism leading to their excess accumulation in cellular compartments, particularly in the lysosome, i.e., lysosomal storage diseases (LSDs). The storage diseases of GSLs and gangliosides affect all organ systems, but the central nervous system (CNS) is primarily involved in many. Current treatments can attenuate the visceral disease, but the management of CNS involvement remains an unmet medical need. Early interventions that alter the CNS disease have shown promise in delaying neurologic involvement in several CNS LSDs. Consequently, effective treatment for such devastating inherited diseases requires an understanding of the early developmental and pathological mechanisms of GSL and ganglioside flux (synthesis and degradation) that underlie the CNS diseases. These are the focus of this review. PMID:20211931

  18. Role of Ce4+ in the scintillation mechanism of codoped Gd3Ga3Al2O12:Ce

    DOE PAGES

    Wu, Yuntao; Meng, Fang; Li, Qi; ...

    2014-10-17

    To control the time-response performance of widely used cerium-activated scintillators in cutting-edge medical-imaging devices, such as time-of-flight positron-emission tomography, a comprehensive understanding of the role of Ce valence states, especially stable Ce4+, in the scintillation mechanism is essential. However, despite some progress made recently, an understanding of the physical processes involving Ce4+ is still lacking. The aim of this work is to clarify the role of Ce4+ in scintillators by studying Ca2+ codoped Gd3Ga3Al2O12∶Ce (GGAG∶Ce). By using a combination of optical absorption spectra and x-ray absorption near-edge spectroscopies, the correlation between Ca2+codoping content and the Ce4+ fraction is seen. The energy-levelmore » diagrams of Ce3+ and Ce4+ in the Gd3Ga3Al2O12 host are established by using theoretical and experimental methods, which indicate a higher position of the 5d1 state of Ce4+ in the forbidden gap in comparison to that of Ce3+. Underlying reasons for the decay-time acceleration resulting from Ca2+ codoping are revealed, and the physical processes of the Ce4+-emission model are proposed and further demonstrated by temperature-dependent radioluminescence spectra under x-ray excitation.« less

  19. Garnet-to-perovskite transition in Gd3Sc2Ga3O12 at high pressure and high temperature.

    PubMed

    Lin, Chuanlong; Liu, Jing; Lin, Jung-Fu; Li, Xiaodong; Li, Yanchun; Zhang, Qingli; Xiong, Lun; Li, Rui

    2013-01-07

    The structural phase transition of gadolinium-scandium-gallium garnet (Gd(3)Sc(2)Ga(3)O(12), GSGG) has been studied at high pressure and high temperature using the synchrotron X-ray diffraction technique in a laser-heated diamond anvil cell. The GSGG garnet transformed to an orthorhombic perovskite structure at approximately 24 GPa after laser heating to 1500-2000 K. The garnet-to-perovskite phase transition is associated with an ∼8% volume reduction and an increase in the coordination number of the Ga(3+) or Sc(3+) ion. The orthorhombic perovskite GSGG has bulk modulus B(0) = 194(15) GPa with B(0)' = 5.3(8), exhibiting slightly less compression than the cubic garnet structure of GSGG with B(0) = 157(15) GPa and B(0)' = 6.5(10). Upon compression at room temperature, the cubic GSGG garnet became amorphous at ∼65 GPa. Coupled with the amorphous-to-perovskite phase transition in Y(3)Fe(5)O(12) and Gd(3)Ga(5)O(12) at high-pressure-temperature conditions, we conclude that amorphization should represent a new thermodynamic state resulting from hindrance of the garnet-to-perovskite phase transition, whereas the garnet-to-amorphous transition in rare-earth garnets should be kinetically hindered at room temperature.

  20. Czochralski growth of Gd3(Al5-xGax)O12 (GAGG) single crystals and their scintillation properties

    NASA Astrophysics Data System (ADS)

    Kurosawa, Shunsuke; Shoji, Yasuhiro; Yokota, Yuui; Kamada, Kei; Chani, Valery I.; Yoshikawa, Akira

    2014-05-01

    Ce:Gd3(AlxGa1-x)5O12 (x=2.5/5 and 3/5, Ce:GAGG-2.5 and Ce:GAGG-3) crystals were grown by the Czochralski process in order to reduce cost of the starting materials as compared with conventional Ce:Gd3Al2Ga3O12 (Ce:GAGG-2) crystal which have high light output. Although perovskite phase was detected in Ce:GAGG-3, Ce:GAGG-2.5 had single-phase garnet structure. Solidification fraction for the Ce:GAGG-2.5 growth was 0.52. Optical properties including transmittance, emission, and excitation spectra of 30 samples cut from the Ce:GAGG-2.5 bulk ingot did not depend on their original position along the growth axis. These samples had light outputs of approximately 58,000±3000 photons/MeV. However, scintillation decay times varied from 140 to 200 ns and depended on the position clearly.

  1. Luminescence and luminescence quenching in Gd3(Ga,Al)5O12 scintillators doped with Ce3+.

    PubMed

    Ogiegło, Joanna M; Katelnikovas, Arturas; Zych, Aleksander; Jüstel, Thomas; Meijerink, Andries; Ronda, Cees R

    2013-03-28

    The optical properties of gadolinium gallium aluminum garnet, Gd3(Ga,Al)5O12, doped with Ce(3+) are investigated as a function of the Ga/Al ratio, aimed at an improved understanding of the energy flow and luminescence quenching in these materials. A decrease of both the crystal field strength and band gap with increasing content of Ga(3+) is observed and explained by the geometrical influence of Ga(3+) on the crystal field splitting of the 5d level in line with theoretical work of Muñoz-García et al. ( uñoz-García, A. B.; Seijo, L. Phys. Rev. B 2010, 82, 184118 ). Thermal quenching results in shorter decay times as well as reduced emission intensities for all samples in the temperature range from 100 to 500 K. An activation energy for emission quenching is calculated from the data. The band gap of the host is measured upon Ga substitution and the decrease in band gap is related to Ga(3+) substitution into tetrahedral sites after all octahedral sites are occupied in the garnet material. Based on the change in band gap and crystal field splitting, band diagrams can be constructed explaining the low thermal quenching temperatures in the samples with high Ga content. The highest luminescence intensity is found for Gd3(Ga,Al)5O12 with 40% of Al(3+) replaced by Ga(3+).

  2. Luminescence Enhanced Eu(3+)/Gd(3+) Co-Doped Hydroxyapatite Nanocrystals as Imaging Agents In Vitro and In Vivo.

    PubMed

    Xie, Yunfei; He, Wangmei; Li, Fang; Perera, Thalagalage Shalika Harshani; Gan, Lin; Han, Yingchao; Wang, Xinyu; Li, Shipu; Dai, Honglian

    2016-04-27

    Biocompatible, biodegradable, and luminescent nano material can be used as an alternative bioimaging agent for early cancer diagnosis, which is crucial to achieve successful treatment. Hydroxyapatite (HAP) nanocyrstals have good biocompatibility and biodegradability, and can be used as an excellent host for luminescent rare earth elements. In this study, based on the energy transfer from Gd(3+) to Eu(3+), the luminescence enhanced imaging agent of Eu/Gd codoping HAP (HAP:Eu/Gd) nanocrystals are obtained via coprecipitation with plate-like shape and no change in crystal phase composition. The luminescence can be much elevated (up to about 120%) with a nonlinear increase versus Gd doping content, which is due to the energy transfer ((6)PJ of Gd(3+) → (5)HJ of Eu(3+)) under 273 nm and the possible combination effect of the cooperative upconversion and the successive energy transfer under 394 nm, respectively. Results demonstrate that the biocompatible HAP:Eu/Gd nanocrystals can successfully perform cell labeling and in vivo imaging. The intracellular HAP:Eu/Gd nanocrystals display good biodegradability with a cumulative degradation of about 65% after 72 h. This biocompatible, biodegradable, and luminescence enhanced HAP:Eu/Gd nanocrystal has the potential to act as a fluorescent imaging agent in vitro and in vivo.

  3. Pathogenic role of ganglioside metabolism in neurodegenerative diseases.

    PubMed

    Ariga, Toshio

    2014-10-01

    Ganglioside metabolism is altered in several neurodegenerative diseases, and this may participate in several events related to the pathogenesis of these diseases. Most changes occur in specific areas of the brain and their distinct membrane microdomains or lipid rafts. Antiganglioside antibodies may be involved in dysfunction of the blood-brain barrier and disease progression in these diseases. In lipid rafts, interactions of glycosphingolipids, including ganglioside, with proteins may be responsible for the misfolding events that cause the fibril and/or aggregate processing of disease-specific proteins, such as α-synuclein, in Parkinson's disease, huntingtin protein in Huntington's disease, and copper-zinc superoxide dismutase in amyotrophic lateral sclerosis. Targeting ganglioside metabolism may represent an underexploited opportunity to design novel therapeutic strategies for neurodegeneration in these diseases. © 2014 Wiley Periodicals, Inc.

  4. Depletion of Gangliosides Enhances Articular Cartilage Repair in Mice

    PubMed Central

    Matsuoka, Masatake; Onodera, Tomohiro; Homan, Kentaro; Sasazawa, Fumio; Furukawa, Jun-ichi; Momma, Daisuke; Baba, Rikiya; Hontani, Kazutoshi; Joutoku, Zenta; Matsubara, Shinji; Yamashita, Tadashi; Iwasaki, Norimasa

    2017-01-01

    Elucidation of the healing mechanisms in damaged tissues is a critical step for establishing breakthroughs in tissue engineering. Articular cartilage is clinically one of the most successful tissues to be repaired with regenerative medicine because of its homogeneous extracellular matrix and few cell types. However, we only poorly understand cartilage repair mechanisms, and hence, regenerated cartilage remains inferior to the native tissues. Here, we show that glycosylation is an important process for hypertrophic differentiation during articular cartilage repair. GM3, which is a precursor molecule for most gangliosides, was transiently expressed in surrounding damaged tissue, and depletion of GM3 synthase enhanced cartilage repair. Gangliosides also regulated chondrocyte hypertrophy via the Indian hedgehog pathway. These results identify a novel mechanism of cartilage healing through chondrocyte hypertrophy that is regulated by glycosylation. Manipulation of gangliosides and their synthases may have beneficial effects on articular cartilage repair. PMID:28252046

  5. The Impact of Gd3+ on DNP of [1-13C]Pyruvate Doped with Trityl OX063, BDPA, or 4-Oxo-TEMPO

    PubMed Central

    Lumata, Lloyd; Merritt, Matthew E.; Malloy, Craig R.; Sherry, A. Dean; Kovacs, Zoltan

    2012-01-01

    Hyperpolarized [1-13C]pyruvate has become an important diagnostic tracer of normal and aberrant cellular metabolism for in vitro and in vivo NMR spectroscopy (MRS) and imaging (MRI). In pursuit of achieving high NMR signal enhancements in dynamic nuclear polarization (DNP) experiments, we have performed an extensive investigation of the influence of Gd3+ doping, a parameter previously reported to improve hyperpolarized NMR signals, on the DNP of this compound. [1-13C]Pyruvate samples were doped with varying amounts of Gd3+ and fixed optimal concentrations of free radical polarizing agents commonly used in fast dissolution DNP: trityl OX063 (15 mM), 4-oxo-TEMPO (40 mM), and BDPA (40 mM). In general, we have observed three regions of interest, namely: (i) a monotonic increase in DNP-enhanced nuclear polarization Pdnp upon increasing the Gd3+ concentration until a certain threshold concentration c1 (1–2 mM) is reached, (ii) a region of roughly constant maximum P from c1 until a concentration threshold c2 (4–5 mM), and (iii) a monotonic decrease in Pdnp at Gd3+ concentration c > c2. Of the three free radical polarizing agents used, trityl OX063 gave the best response to Gd3+ doping with a 300 % increase in the solid-state nuclear polarization whereas addition of the optimum Gd3+ concentration on BDPA and 4-oxo-TEMPO-doped samples only yielded a relatively modest 5–20 % increase in the base DNP-enhanced polarization. The increase in Pdnp due to Gd3+ doping is ascribed to the decrease in the electronic spin-lattice relaxation T1e of the free radical electrons which plays a role in achieving lower spin temperature Ts of the nuclear Zeeman system. These results are discussed qualitatively in terms of the spin temperature model of DNP. PMID:22571288

  6. Synthesis and cytotoxicity assay of four ganglioside GM3 analogues.

    PubMed

    Qu, Huanhuan; Liu, Jian-Miao; Wdzieczak-Bakala, Joanna; Lu, Dan; He, Xianran; Sun, Wenji; Sollogoub, Matthieu; Zhang, Yongmin

    2014-03-21

    A concise and efficient synthetic route for preparation of four ganglioside GM3 analogues was described. The key step is a highly regioselective and stereoselective α-sialylation from a suitably protected glycoside acceptor with a sialyl xanthate to provide the sialo-oligosaccharide in good yield. The cytotoxic properties of the synthetic gangliosides were evaluated against normal human keratinocytes and human HCT116 and K562 cancer cells. Two of them exhibited good antiproliferative activity and displayed a better cytotoxicity against cancer cell than HaCaT normal cell. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  7. GM1 and GM2 gangliosides: recent developments.

    PubMed

    Bisel, Blaine; Pavone, Francesco S; Calamai, Martino

    2014-03-01

    GM1 and GM2 gangliosides are important components of the cell membrane and play an integral role in cell signaling and metabolism. In this conceptual overview, we discuss recent developments in our understanding of the basic biological functions of GM1 and GM2 and their involvement in several diseases. In addition to a well-established spectrum of disorders known as gangliosidoses, such as Tay-Sachs disease, more and more evidence points at an involvement of GM1 in Alzheimer's and Parkinson's diseases. New emerging methodologies spanning from single-molecule imaging in vivo to simulations in silico have complemented standard studies based on ganglioside extraction.

  8. The role of gangliosides in brain development and the potential benefits of perinatal supplementation.

    PubMed

    Ryan, Jennifer M; Rice, Gregory E; Mitchell, Murray D

    2013-11-01

    The maternal diet provides critical nutrients that can influence fetal and infant brain development and function. This review highlights the potential benefits of maternal dietary ganglioside supplementation on fetal and infant brain development. English-language systematic reviews, preclinical studies, and clinical studies were obtained through searches on PubMed. Reports were selected if they included benefits and harms of maternal ganglioside supplementation during pregnancy or ganglioside-supplemented formula after pregnancy. The potential benefits of ganglioside supplementation were explored by investigating the following: (1) their role in neural development, (2) their therapeutic use in neural injury and disease, (3) their presence in human breast milk, and (4) their use as a dietary supplement during or after pregnancy. Preclinical studies indicate that ganglioside supplementation at high doses (1% of total dietary intake) can significantly increase cognitive development and body weight when given prenatally. However, lower ganglioside supplementation doses have no beneficial cognitive effects, even when given throughout pregnancy and lactation. In human clinical trials, infants given formula supplemented with gangliosides showed increased cognitive development and an increase in ganglioside content. Ganglioside supplementation may promote brain development and function in offspring when administered at the optimum dosage. We propose that prenatal maternal dietary supplementation with gangliosides throughout pregnancy may promote greater long-term effects on brain development and function. Before this concept can be encouraged in preconception clinics, future research and clinical trials are needed to confirm the ability of dietary gangliosides to improve cognitive development, but available results already encourage this area of research.

  9. Altered expression of ganglioside GM3 molecular species and a potential regulatory role during myoblast differentiation.

    PubMed

    Go, Shinji; Go, Shiori; Veillon, Lucas; Ciampa, Maria Grazia; Mauri, Laura; Sato, Chihiro; Kitajima, Ken; Prinetti, Alessandro; Sonnino, Sandro; Inokuchi, Jin-Ichi

    2017-04-28

    Gangliosides (sialic acid-containing glycosphingolipids) help regulate many important biological processes, including cell proliferation, signal transduction, and differentiation, via formation of functional microdomains in plasma membranes. The structural diversity of gangliosides arises from both the ceramide moiety and glycan portion. Recently, differing molecular species of a given ganglioside are suggested to have distinct biological properties and regulate specific and distinct biological events. Elucidation of the function of each molecular species is important and will provide new insights into ganglioside biology. Gangliosides are also suggested to be involved in skeletal muscle differentiation; however, the differential roles of ganglioside molecular species remain unclear. Here we describe striking changes in quantity and quality of gangliosides (particularly GM3) during differentiation of mouse C2C12 myoblast cells and key roles played by distinct GM3 molecular species at each step of the process. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Antibodies to gangliosides and ganglioside complexes in Guillain-Barré syndrome and Fisher syndrome: mini-review.

    PubMed

    Kaida, Kenichi; Kusunoki, Susumu

    2010-06-01

    Antiganglioside antibodies play a pathogenic role in the pathophysiology of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS). Antiganglioside antibody-mediated nerve injury is likely to result from nerve damage through complement activation or dysfunction of molecules such as voltage-gated sodium and calcium channels. Clustered epitopes of complexes of two gangliosides in the cell membrane can be targeted by serum antibodies in GBS and FS and may regulate the accessibility and avidity of antiganglioside antibodies. The glycolipid environment or the specific distribution of target gangliosides in the peripheral nervous system may also influence the pathogenic effect of antiganglioside antibodies in GBS and FS. Structural and functional analyses of glycoepitopes of ganglioside complexes in membranes will provide new vistas on antibody-antigen interaction in GBS and shed light on microdomain function mediated by carbohydrate-carbohydrate interactions, which may lead to novel treatments for GBS and FS. Copyright 2010 Elsevier B.V. All rights reserved.

  11. [The regulation of ganglioside GM3 synthesis].

    PubMed

    Uemura, Satoshi

    2012-01-01

    Glycosphingolipids (GSLs) exist in the outer leaflet of the plasma membrane, where they form lipid microdomains that function as platforms for the regulation of trans-membrane signal transduction. In mammals, complex GSLs differing in the number and/or type of sugar species are produced in a cell-type specific manner, and the variety of glycan structures in GSLs are believed to determine specific cell functions. The glycan moieties of GSLs are synthesized at the luminal side of the Golgi apparatus by multiple Golgi-resident glycosyltransferases. Since the expression levels of most endogenous glycosyltransferases are relatively low, their detection is generally difficult. Nevertheless, we have succeeded in detecting endogenous mouse GM3 synthase (GM3S), the primary glycosyltransferase responsible for the biosynthesis of ganglio-series gangliosides. Mouse GM3S (mGM3S) has three isoforms (M1-GM3S, M2-GM3S, and M3-GM3S), each with a distinct length in its NH2-terminal cytoplasmic tail. These isoforms are produced by leaky scanning from two mRNA variants, mGM3Sa and mGM3Sb. M1-GM3S is stably localized in the endoplasmic reticulum (ER), as a result of retrograde transport signals (arginine [R]-based motifs); consequently, its in vivo GM3 synthesis activity is very low compared with that of other isoforms. In contrast, both M2-GM3S and M3-GM3S are localized in the Golgi apparatus, yet each exhibits a distinct intracellular fate. M2-GM3S is rapidly degraded in the lysosomes, whereas M3-GM3S is retained in the Golgi apparatus. A system that produces GM3S isoforms having such distinct characteristics is likely to be of critical importance in the regulation of GM3 biosynthesis under various pathological and physiological conditions.

  12. Magnetic and magnetocaloric properties of the new rare-earth-transition-metal intermetallic compound Gd3Co29Ge4B10

    NASA Astrophysics Data System (ADS)

    Hill, P.; Dubenko, Igor; Samanta, Tapas; Quetz, Abdiel; Ali, Naushad

    2012-04-01

    The compounds Gd3-xYxCo29Ge4B10 (x = 0, 0.5, 1.0, 1.5, and 3.0), Gd3Co29Al4B10, and Gd3Co29Al4B10 were synthesized by arc melting, and their magnetic properties investigated as a function of temperature and applied magnetic field. X-ray measurements showed primarily single-phase samples with the tetragonal crystal structure P4/nmm. It was found that Gd3Co29Ge4B10 orders ferromagnetically at TC = 212 K and shows a compensation point at 128 K, indicating a ferrimagnetic ordering of the Co and Gd moments. An entropy change of -ΔS = 0.5 J/kgK was observed in a 5-T field at TC for this sample, while a change in sign for this quantity was observed both at the maximum value of magnetization (around 200 K) and then again at the compensation point. Substitution of Y for Gd in Gd3Co29Ge4B10 does not affect the Curie temperature, but shifts the compensation point to lower temperatures. This indicates that a decrease in Gd concentration does not affect the d-d exchange interaction, but has a pronounced effect on the f-d exchange interaction.

  13. Broadband Yellowish-Green Emitting Ba4Gd3Na3(PO4)6F2:Eu(2+) Phosphor: Structure Refinement, Energy Transfer, and Thermal Stability.

    PubMed

    Fu, Xiaopeng; Lü, Wei; Jiao, Mengmeng; You, Hongpeng

    2016-06-20

    A series of Ba4Gd3Na3(PO4)6F2:Eu(2+) phosphors with a broad emitting band have been synthesized by a traditional solid state reaction. The crystal structural and photoluminescence properties of Ba4Gd3Na3(PO4)6F2:Eu(2+) are investigated. The different crystallographic sites of Eu(2+) in Ba4Gd3Na3(PO4)6F2:Eu(2+) phosphors have been verified by means of their photoluminescence (PL) properties and decay times. Energy transfer between Eu(2+) ions, analyzed by excitation, emission, and PL decay behavior, has been indicated to be a dipole-dipole mechanism. Moreover, the luminescence quantum yield as well as the thermal stability of the Ba4Gd3Na3(PO4)6F2:Eu(2+) phosphor have been investigated systematically. The as-prepared Ba4Gd3Na3(PO4)6F2:Eu(2+) phosphor can act as a promising candidate for n-UV convertible white LEDs.

  14. The gadolinium nitride selenides Gd3NSe3 and Gd23N5Se27: Three connectivity types of [NGd4]9+ tetrahedra and fivefold coordinated Gd3+ cations

    NASA Astrophysics Data System (ADS)

    Schurz, Christian M.; Talmon-Gros, Pia; Lissner, Falk; Schleid, Thomas

    2013-03-01

    The gadolinium nitride selenides Gd3NSe3 and Gd23N5Se27 are formed by the reaction of gadolinium metal with its triiodide, cesium azide and selenium along with an excess of cesium iodide as flux within seven days at 900 °C in torch-sealed evacuated silica ampoules. The dominant phase Gd3NSe3 crystallizes isotypically with Sm3NS3 in the orthorhombic space group Pnma (unit cell: a = 1256.71(9) pm, b = 398.65(3) pm, c = 1318.32(9) pm, Z = 4). Thus nitride-centered (Gd4)12+ tetrahedra are linked via two vertices each forming {[}∞1 chains (t = terminal, v = vertex-shared) along [010], which become interconnected by three crystallographically different Se2- anions. Beside C-type of Gd2Se3 and at least another unknown phase powder diffraction experiments show additional reflections indicating the second nitride selenide Gd23N5Se27. This new compound crystallizes non-centrosymmetrically in the monoclinic space group Pc (unit cell: a = 2854.87(19) pm, b = 1227.94(8) pm, c = 747.62(5) pm, β = 94.215(3)°, Z = 2). Here, {(}∞2 and {(}∞2 layers embed the main structural features of isolated [NGd4]9+ tetrahedra and isolated congonial [N2Gd6]12+ bitetrahedra. Another particularity is the fivefold coordination of the (Gd4)3+ cations with one short contact to N3- and four relatively short bonds to four Se2- anions, respectively.

  15. Resonant inelastic X-ray scattering at the L 3 edge of Eu 2+, Gd 3+, and Tb 4+ compounds

    NASA Astrophysics Data System (ADS)

    Dallera, C.; Krisch, M.; Rogalev, A.; Goulon, J.; Sette, F.

    2002-03-01

    4d→2p inelastic X-ray scattering (IXS) spectra of Eu2+, Gd3+ and Tb4+ compounds, resonantly enhanced at the rare-earth L3 absorption edge, are presented. Despite their common 8S7/2 (4f7) ground state, the RIXS spectra display strong differences, arising from the different energy separation between the dipolar (E1) and quadrupolar (E2) excitation channels, and the 5d crystal field splitting. The quantitative determination of these energy separations provides further experimental input for the correct interpretation of X-ray Magnetic Circular Dichroism (XMCD) experiments performed at the L2,3 edges of the rare-earth compounds.

  16. The Exchange Coupling of Gd3+- and Cr3+-Ions in Paramagnetic GdCrO3 (In German)

    NASA Astrophysics Data System (ADS)

    Dräger, K.

    1986-03-01

    Polycrystalline samples of stoichiometric GdCrO3 have been investigated by ESR at 9.4 GHz. In the temperature range between 175 K and 520 K one broad absorption with a Lorentzian line shape and a g-factor of 2.024 has been observed. Attributing the absorption exclusively to the Gd -ion it can be shown that the temperature dependence of the ESR-intensity follows the predictions of a cluster-model. The energy describing the coupling of a single Gd3+-ion to the surrounding Cr3+-ions is found to be ΔE(Gd) = 170 cm-1. Taking advantage of the similarity within the orthochromites it is possible to determine at the same time the exchange - coupling of Cr3+-ions to their identical nearest neighbours as ΔE(Cr) = 293 cm-1. The relative strength of these couplings given by 0.60 is compatible with other experimental issues.

  17. Mechanochemical preparation of nanocrystalline NaYF4:Gd3+/Yb3+/Tm3+: An efficient upconversion phosphor

    NASA Astrophysics Data System (ADS)

    Zhang, Jun; Riesen, Hans

    2015-11-01

    We report on a mechanochemical preparation route for NaYF4:Gd3+/Yb3+/Tm3+ nanoparticles by ball-milling NaF, YF3, GdF3, YbF3 and TmF3 at room temperature. An analysis by XRD and TEM demonstrates that the resulting materials are mainly (∼88% after 4 h ball-milling) in the hexagonal phase and are on the nanoscale with an average crystallite size of ∼20 nm. The prepared nanoparticles display efficient upconversion emission; upon excitation by a 980 nm laser diode, bright visible blue light emission can be observed. However, in accord with previous results, the strongest emission is observed in the NIR at 800 nm.

  18. Gd3+ doped Mn-Zn soft ferrite nanoparticles: Superparamagnetism and its correlation with other physical properties

    NASA Astrophysics Data System (ADS)

    Thakur, Prashant; Sharma, Rohit; Sharma, Vineet; Barman, P. B.; Kumar, Manoj; Barman, Dipto; Katyal, S. C.; Sharma, Pankaj

    2017-06-01

    Superparamagnetic nanoparticles are very important in biomedicine due to their various applications like drug delivery, gene delivery in the body and also used for hyperthermia. In the present work, superparamagnetic nanoparticles of Mn0.5Zn0.5GdxFe2-xO4 (x = 0, 0.025, 0.050, 0.075, 0.1) ferrites have been prepared by co-precipitation method. Thorough characterizations (XRD, FTIR, FE-SEM, EDS, VSM and fluorescence spectroscopy) have proved the formation of cubical spinel superparamagnetic nanoparticles of soft ferrites. A cation distribution has been proposed for the determination of various important theoretical parameters for these samples. With the addition of Gd3+ nanoparticles have shown the superparamagnetism at room temperature confirmed by VSM analysis. Photoluminescence (PL) spectra shows a blue shift (for x = 0.025, 0.075) which may be due to quantum confinement.

  19. Continuous-wave laser operation of diode-pumped Tm-doped Gd3Ga5O12 crystal

    NASA Astrophysics Data System (ADS)

    Wang, Yi; Lan, Jinglong; Zhou, Zhiyong; Guan, Xiaofeng; Xu, Bin; Xu, Huiying; Cai, Zhiping; Wang, Yan; Tu, Chaoyang

    2017-04-01

    We report on a diode-pumped Tm:Gd3Ga5O12 (GGG) laser at 2004 nm operated in continuous-wave mode with two-mirror linear cavity configuration. The maximum output power reaches 0.58 W with laser threshold absorbed pump power of about 0.39 W and overall slope efficiency of about 18.4%, which is believed to be the highest output power for Tm:GGG laser up to now. The Tm:GGG laser shows obvious thermally induced saturation of the output power, which indicated that power and efficiency scaling could be furtherly realized by more efficient thermal removal of the laser crystal.

  20. Fabrication of Ce3+ doped Gd3Ga3Al2O12 ceramics by reactive sintering method

    NASA Astrophysics Data System (ADS)

    Ye, Yong; Liu, Peng; Yan, Dongyue; Xu, Xiaodong; Zhang, Jian

    2017-09-01

    Ce3+ doped Gd3Ga3Al2O12 (Ce:GGAG) ceramics were fabricated by solid state reactive sintering method in this study. The ceramics were pre-sintered in normal muffle furnace in air at various temperature range from 1410 °C to 1550 °C for 10 h and post-treated by hot isostatic press at 1400 °C/2 h in 200 MPa Ar. The phase and microstructure evolution of Ce: GGAG samples during the densification process were investigated by X-ray diffraction and scanning electron microscope. Pure GGAG phase appeared with the temperature increased to 1200 °C. The fully dense and translucent GGAG ceramics were fabricated by pre-sintering at 1450 °C and followed by HIP treatment.

  1. Ganglioside inserted into PEGylated liposome attenuates anti-PEG immunity.

    PubMed

    Mima, Yu; Abu Lila, Amr S; Shimizu, Taro; Ukawa, Masami; Ando, Hidenori; Kurata, Yasuko; Ishida, Tatsuhiro

    2017-03-28

    Despite the clinical introduction of a vast number of polyethylene glycol (PEG)-conjugated therapeutics, conjugated PEG is also known for an unfortunate inclination toward immunogenicity. Immunogenicity of PEG, manifested by the robust production of anti-PEG IgM, is known to compromise the therapeutic efficacy and/or reduce the tolerance of PEGylated therapeutics. In the present study, we inserted ganglioside into the membrane of PEGylated liposome (PL) to prepare ganglioside-modified PEGylated liposomes (G-PL), and investigated its efficacy in attenuating the anti-PEG IgM response against PL. A single intravenous injection of G-PL significantly attenuated the anti-PEG IgM production, compared with that of naïve PL. In addition, pretreatment with G-PL substantially alleviated the anti-PEG IgM response elicited by a subsequent dose of PL, presumably via inducing B cell tolerance, and as a consequence, this modification abrogated/attenuated the incidence of the rapid clearance of subsequently administrated PL. These results indicate that incorporating gangliosides in PEGylated liposome membrane not only prevents the immunogenicity of PEG but also induces the tolerance of B cells to subsequent doses of the immunogenic PL. Consequently, liposomal membrane modification with ganglioside might represent a promising approach to attenuating the immunogenicity of PEGylated liposomes while preserving their therapeutic efficacy, particularly upon repeated administration.

  2. Exogenous gangliosides may affect methylation mechanisms in neuronal cell cultures

    SciTech Connect

    Ferret, B.; Hubsch, A.; Dreyfus, H.; Massarelli, R. )

    1991-02-01

    Primary neurons in culture from chick embryo cerebral hemispheres were treated with a mixture of gangliosides added to the growth medium (final concentration: 10(-5)M and 10(-8)M) from the 3rd to the 6th day in vitro. Under these conditions methylation processes measured with (3H) and (35S) methionine and (3H)ethanolamine as precursors showed an increased methylation of (3H)ethanolamine containing phospholipids, a correspondent increased conversion of these compounds to (3H)choline containing phospholipids, and a general increased methylation of trichloroacetic acid precipitable macromolecules containing labeled methionine. A small increase in protein synthesis was observed after incubation of neurons with (3H)- and (35S)methionine. This was confirmed after electrophoretic separation of a protein extract with increased 3H- and 35S-labeling in protein bands with moecular weights between 50 and 60 KDaltons. A protein band of about 55 KDaltons appeared to be preferentially labelled when (3H) methionine was the precursor. The treatment with gangliosides increased the incorporation of (methyl-3H) label after incubation of neurons with (3H) methionine, into total DNA and decreased that of total RNA. The treatment of neurons in culture with exogenous gangliosides hence affects differently methylation processes, a finding which may confirm the involvement of gangliosides on the intracellular mediation of neuronal information mechanisms.

  3. Atomistic study on the site preference and lattice vibration of Gd3-xYxCo29T4B10 (T=Al and Ge)

    NASA Astrophysics Data System (ADS)

    Cheng, Hai-Xia; Wang, Xiao-Xu; Hu, Yao-Wen; Zhang, Guo-Hua; Shen, Jiang; Qian, Ping; Chen, Nan-Xian

    2015-04-01

    The effects of the Y substitution for Gd on the structural stability and the site preference of intermetallics Gd3-xYxCo29T4B10 (T=Al and Ge) are studied by using a series of interatomic pair potentials. The calculated results show Y can stabilize Gd3-xYxCo29T4B10 with the tetragonal structure, and Y substitute for Gd with a strong preference for the 2b sites. The calculated lattice parameters are in good agreement with the experimental data. Furthermore, the total and partial phonon densities of states are evaluated for the Gd3-xYxCo29T4B10 compounds with the tetragonal structure. A qualitative analysis is carried out with the relevant potentials for the vibrational modes, which makes it possible to predict some properties related to lattice vibration.

  4. Anti-Ganglioside Antibodies in Amyotrophic Lateral Sclerosis Revisited

    PubMed Central

    Kollewe, Katja; Wurster, Ulrich; Sinzenich, Thomas; Körner, Sonja; Dengler, Reinhard; Mohammadi, Bahram; Petri, Susanne

    2015-01-01

    Background Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder with typical onset in the 5th- 6th decade of life. The hypothesis of an autoimmune origin of ALS receives less attention today, but immunological phenomena still seem to be involved and mechanisms such as protective autoimmunity may be important. Detection of antibodies against a variety of gangliosides has been repeatedly described in ALS-patients by several authors, but widely differing frequencies and titres have been reported. Therefore, we investigated the presence of six common antibodies with a commercially available test panel for GA1, GM1, GM2, GD1a, GD1b and GQ1b in a large group of clinically well-characterized ALS patients and compared them to a collective of 200 healthy blood donors. Methods IgG and IgM antibodies to the six gangliosides asialoGM1 (GA1), GM1, GM2, GD1a, GD1b, GQ1b were determined by GanglioCombi ELISA in sera of 84 ALS patients. Results were expressed as a %-ratio of a highly positive control and categorized as negative (<30%), borderline (30–50%), moderately (50–100%) and strongly positive (>100%). The values obtained from 200 Swiss blood donors served as a reference group. Results In twenty-two (26.2%) ALS-patients elevated anti-ganglioside antibodies could be detected: Taking all subspecific antibodies together, IgG antibodies were found in 9/84 (10.7%) and IgM in 15/84 (17.9%) patients. There was no correlation between age, gender, site of onset or survival and anti-ganglioside-positive/-negative titres in ALS-patients. No statistically significant difference in the frequency of anti-ganglioside antibodies compared to the group of healthy blood donors was found. Conclusion Even with this more comprehensive approach, anti-ganglioside antibody frequencies and patterns in our ALS cohort closely resembled the values measured in healthy controls. In accordance with other studies, we did not observe any association of a distinct ALS phenotype

  5. Anti-ganglioside antibodies in amyotrophic lateral sclerosis revisited.

    PubMed

    Kollewe, Katja; Wurster, Ulrich; Sinzenich, Thomas; Körner, Sonja; Dengler, Reinhard; Mohammadi, Bahram; Petri, Susanne

    2015-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder with typical onset in the 5th- 6th decade of life. The hypothesis of an autoimmune origin of ALS receives less attention today, but immunological phenomena still seem to be involved and mechanisms such as protective autoimmunity may be important. Detection of antibodies against a variety of gangliosides has been repeatedly described in ALS-patients by several authors, but widely differing frequencies and titres have been reported. Therefore, we investigated the presence of six common antibodies with a commercially available test panel for GA1, GM1, GM2, GD1a, GD1b and GQ1b in a large group of clinically well-characterized ALS patients and compared them to a collective of 200 healthy blood donors. IgG and IgM antibodies to the six gangliosides asialoGM1 (GA1), GM1, GM2, GD1a, GD1b, GQ1b were determined by GanglioCombi ELISA in sera of 84 ALS patients. Results were expressed as a %-ratio of a highly positive control and categorized as negative (<30%), borderline (30-50%), moderately (50-100%) and strongly positive (>100%). The values obtained from 200 Swiss blood donors served as a reference group. In twenty-two (26.2%) ALS-patients elevated anti-ganglioside antibodies could be detected: Taking all subspecific antibodies together, IgG antibodies were found in 9/84 (10.7%) and IgM in 15/84 (17.9%) patients. There was no correlation between age, gender, site of onset or survival and anti-ganglioside-positive/-negative titres in ALS-patients. No statistically significant difference in the frequency of anti-ganglioside antibodies compared to the group of healthy blood donors was found. Even with this more comprehensive approach, anti-ganglioside antibody frequencies and patterns in our ALS cohort closely resembled the values measured in healthy controls. In accordance with other studies, we did not observe any association of a distinct ALS phenotype with elevated anti-ganglioside antibodies

  6. Highly biocompatible TiO2:Gd3+ nano-contrast agent with enhanced longitudinal relaxivity for targeted cancer imaging

    NASA Astrophysics Data System (ADS)

    Chandran, Parwathy; Sasidharan, Abhilash; Ashokan, Anusha; Menon, Deepthy; Nair, Shantikumar; Koyakutty, Manzoor

    2011-10-01

    We report the development of a novel magnetic nano-contrast agent (nano-CA) based on Gd3+ doped amorphous TiO2 of size ~25 nm, exhibiting enhanced longitudinal relaxivity (r1) and magnetic resonance (MR) contrasting together with excellent biocompatibility. Quantitative T1 mapping of phantom samples using a 1.5 T clinical MR imaging system revealed that the amorphous phase of doped titania has the highest r1 relaxivity which is ~2.5 fold higher than the commercially used CA Magnevist™. The crystalline (anatase) samples formed by air annealing at 250 °C and 500 °C showed significant reduction in r1 values and MR contrast, which is attributed to the loss of proton-exchange contribution from the adsorbed water and atomic re-arrangement of Gd3+ ions in the crystalline host lattice. Nanotoxicity studies including cell viability, plasma membrane integrity, reactive oxygen stress and expression of pro-inflammatory cytokines, performed on human primary endothelial cells (HUVEC), human blood derived peripheral blood mononuclear cells (PBMC) and nasopharyngeal epidermoid carcinoma (KB) cell line showed excellent biocompatibility up to relatively higher doses of 200 μg ml-1. The potential of this nano-CA to cause hemolysis, platelet aggregation and plasma coagulation were studied using human peripheral blood samples and found no adverse effects, illustrating the possibility of the safe intravenous administration of these agents for human applications. Furthermore, the ability of these agents to specifically detect cancer cells by targeting molecular receptors on the cell membrane was demonstrated on folate receptor (FR) positive oral carcinoma (KB) cells, where the folic acid conjugated nano-CA showed receptor specific accumulation on cell membrane while leaving the normal fibroblast cells (L929) unstained. This study reveals that the Gd3+ doped amorphous TiO2 nanoparticles having enhanced magnetic resonance contrast and high biocompatibility is a promising candidate for

  7. MALDI mass spectrometry imaging of gangliosides in mouse brain using ionic liquid matrix.

    PubMed

    Chan, Kenneth; Lanthier, Patricia; Liu, Xin; Sandhu, Jagdeep K; Stanimirovic, Danica; Li, Jianjun

    2009-04-20

    Mass spectrometry imaging has emerged as a powerful tool for the direct detection of biomolecules, mainly phospholipids, proteins and peptides, in tissue samples. To date, there is very little information available on the direct analysis of gangliosides in brain tissue. One major hurdle for imaging gangliosides in tissue using mass spectrometry is that sialic acid residues can be dissociated in ionization process. In this report, we investigated an ionic liquid matrix for mass spectrometry imaging of gangliosides. This ionic liquid matrix offered excellent sensitivity for detection gangliosides without significant loss of sialic acid residues. Thus, it can be used to study the abundance and anatomical localization of gangliosides in mouse brain using mass spectrometry imaging technique. Mass spectrometry image analyses of the mouse brain tissue sections demonstrated that the N-fatty acyl chains of gangliosides were differentially distributed in mouse hippocampal regions, whereby the gangliosides with N-C(18) acyl chain were enriched in CA1 region, while gangliosides with N-C(20) acyl chain were enriched in dentate gyrus. In addition, this observation is true for mono-, di- and tri-sialylated gangliosides. Although the linkage information was not determined, the mass spectrometry imaging technique was capable of spatial tissue mapping of ceramide structures in gangliosides.

  8. Major and c-series gangliosides in lenticular tissues: mammals to molluscs.

    PubMed

    Saito, M; Sugiyama, K

    2001-10-01

    Gangliosides of eye lenses were examined in mammals (rat, rabbits, pig, cow), bird (chicken), reptile (terrapin), amphibian (bullfrog), bony fish (red sea bream, bluefin tuna, bonito, Pacific mackerel) and molluscs (common squid, Pacific octopus). Besides the fact that GM3 was the common ganglioside species, the composition of major gangliosides in mammalian eye lenses significantly differed from each other. While gangliotetraose gangliosides were abundant in rat eye lens, they did not constitute major components in porcine and bovine tissues. The c-series ganglioside GT3 was expressed in rat eye lenses but were practically absent in other mammalian tissues. The composition of major gangliosides in eye lenses of lower animals varied from species to species, whereas c-series gangliosides were consistently expressed, showing similar compositional profiles. Our results demonstrate the species-specific compositions of lenticular gangliosides. Evidence was also provided suggesting that eye lenses of common squid (Todarodes pacificus) and Pacific octopus (Octopus vulgaris) express gangliosides including gangliotetraose species and c-series gangliosides.

  9. Unique gangliosides synthesized in vitro by sialyltransferases from marine bacteria and their characterization: ganglioside synthesis by bacterial sialyltransferases

    PubMed Central

    Kamimiya, Hisashi; Suzuki, Yusuke; Kasama, Takeshi; Kajiwara, Hitomi; Yamamoto, Takeshi; Mine, Toshiki; Watarai, Shinobu; Ogura, Kiyoshi; Nakamura, Kazuo; Tsuge, Junichi; Kushi, Yasunori

    2013-01-01

    On the basis of the results outlined in our previous report, bacterial sialyltransferases (ST) from marine sources were further characterized using glycosphingolipids (GSL), especially ganglio-series GSLs, based on the enzymatic characteristics and kinetic parameters obtained by Line weaver-Burk plots. Among them, GA1 and GA2 were found to be good substrates for these unique STs. Thus, new gangliosides synthesized by α2-3 and α2-6STs were structurally characterized by several analytical procedures. The ganglioside generated by the catalytic activity of α2-3ST was identified as GM1b. On the other hand, when enzyme reactions by α2-6STs were performed using substrates GA2 and GA1, very unique gangliosides were generated. The structures were identified as NeuAcα2-6GalNAcβ1-4Galβ1-4Glcβ-Cer and NeuAcα2-6Galβ1-3GalNAcβ1-4Galβ1-4Glcβ-Cer, respectively. The synthesized ganglioside NeuAcα2-6GalNAcβ1-4Galβ1-4Glcβ-Cer showed binding activity to the influenza A virus {A/Panama/2007/99 (H3N2)} at a similar level to purified sialyl(α2-3)paragloboside (S2-3PG) and sialyl(α2-6)paragloboside (S2-6PG) from mammalian sources. The evidence suggests that these STs have unique features, including substrate specificities restricted not only to lacto-series but also to ganglio-series GSLs, as well as catalytic potentials for ganglioside synthesis. This evidence demonstrates that effective in vitro ganglioside synthesis could be a valuable tool for selectively synthesizing sialic acid (Sia) modifications, thereby preparing large-scale gangliosides and permitting the exploration of unknown functions. PMID:23220479

  10. Unique gangliosides synthesized in vitro by sialyltransferases from marine bacteria and their characterization: ganglioside synthesis by bacterial sialyltransferases.

    PubMed

    Kamimiya, Hisashi; Suzuki, Yusuke; Kasama, Takeshi; Kajiwara, Hitomi; Yamamoto, Takeshi; Mine, Toshiki; Watarai, Shinobu; Ogura, Kiyoshi; Nakamura, Kazuo; Tsuge, Junichi; Kushi, Yasunori

    2013-03-01

    On the basis of the results outlined in our previous report, bacterial sialyltransferases (ST) from marine sources were further characterized using glycosphingolipids (GSL), especially ganglio-series GSLs, based on the enzymatic characteristics and kinetic parameters obtained by Line weaver-Burk plots. Among them, GA1 and GA2 were found to be good substrates for these unique STs. Thus, new gangliosides synthesized by α2-3 and α2-6STs were structurally characterized by several analytical procedures. The ganglioside generated by the catalytic activity of α2-3ST was identified as GM1b. On the other hand, when enzyme reactions by α2-6STs were performed using substrates GA2 and GA1, very unique gangliosides were generated. The structures were identified as NeuAcα2-6GalNAcβ1-4Galβ1-4Glcβ-Cer and NeuAcα2-6Galβ1-3GalNAcβ1-4Galβ1-4Glcβ-Cer, respectively. The synthesized ganglioside NeuAcα2-6GalNAcβ1-4Galβ1-4Glcβ-Cer showed binding activity to the influenza A virus {A/Panama/2007/99 (H3N2)} at a similar level to purified sialyl(α2-3)paragloboside (S2-3PG) and sialyl(α2-6)paragloboside (S2-6PG) from mammalian sources. The evidence suggests that these STs have unique features, including substrate specificities restricted not only to lacto-series but also to ganglio-series GSLs, as well as catalytic potentials for ganglioside synthesis. This evidence demonstrates that effective in vitro ganglioside synthesis could be a valuable tool for selectively synthesizing sialic acid (Sia) modifications, thereby preparing large-scale gangliosides and permitting the exploration of unknown functions.

  11. 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

    NASA Astrophysics Data System (ADS)

    Zamfir, Alina D.; Serb, Alina; Vukeli, Željka; Flangea, Corina; Schiopu, Catalin; Fabris, Dragana; Kalanj-Bognar, Svjetlana; Capitan, Florina; Sisu, Eugen

    2011-12-01

    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 age-matched 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 N-acetylneuraminic 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 collision-induced 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.

  12. Cancer vaccines: an update with special focus on ganglioside antigens.

    PubMed

    Bitton, Roberto J; Guthmann, Marcel D; Gabri, Mariano R; Carnero, Ariel J L; Alonso, Daniel F; Fainboim, Leonardo; Gomez, Daniel E

    2002-01-01

    Vaccine development is one of the most promising and exciting fields in cancer research; numerous approaches are being studied to developed effective cancer vaccines. The aim of this form of therapy is to teach the patient's immune system to recognize the antigens expressed in tumor cells, but not in normal tissue, to be able to destroy these abnormal cells leaving the normal cells intact. In other words, is an attempt to teach the immune system to recognize antigens that escaped the immunologic surveillance and are by it, therefore able to survive and, in time, disseminate. However each research group developing a cancer vaccine, uses a different technology, targeting different antigens, combining different carriers and adjuvants, and using different immunization schedules. Most of the vaccines are still experimental and not approved by the US or European Regulatory Agencies. In this work, we will offer an update in the knowledge in cancer immunology and all the anticancer vaccine approaches, with special emphasis in ganglioside based vaccines. It has been demonstrated that quantitative and qualitative changes occur in ganglioside expression during the oncogenic transformation. Malignant transformation appears to activate enzymes associated with ganglioside glycosylation, resulting in altered patterns of ganglioside expression in tumors. Direct evidence of the importance of gangliosides as potential targets for active immunotherapy has been suggested by the observation that human monoclonal antibodies against these glycolipids induce shrinkage of human cutaneous melanoma metastasis. Thus, the cellular over-expression and shedding of gangliosides into the interstitial space may play a central role in cell growth regulation, immune tolerance and tumor-angiogenesis, therefore representing a new target for anticancer therapy. Since 1993 researchers at the University of Buenos Aires and the University of Quilmes (Argentina), have taken part in a project carried out by

  13. Nervous system ganglioside composition of normothermic and hibernating dormice (Glis glis).

    PubMed

    Sonnino, S; Ghidoni, R; Malesci, A; Tettamanti, G; Marx, J; Hilbig, R; Rahmann, H

    1984-01-01

    The ganglioside pattern of seven different regions, olfactory bulb, forebrain cortex, midbrain (corpora quadrigemina), cerebellum, brain stem, pons and spinal cord, of nervous system of normothermic and hibernating dormice (Glis glis) were investigated by two dimensional thin layer chromatography and densitometric quantification. Up to thirty different ganglioside spots were resolved, fifteen of which belonging to alkali labile species. Alkali labile gangliosides were present in all the regions obtained from normothermic animals, and their content, expressed as percentage of total ganglioside-bound sialic acid, ranged from a minimum of 10.2% in olfactory bulb, to a maximum of 30.1% in spinal cord. The most abundant alkali labile gangliosides were O-Ac-GT1b, O-Ac-GQ1b and an unidentified one, we coded I3. Alkali labile gangliosides were practically undetectable in hibernating dormice. They could be recognized only in brain stem, 3.3% and olfactory bulb, 0.6%.

  14. Gangliosides and sialosylglycoproteins in coated vesicles from bovine brain.

    PubMed Central

    Gravotta, D; Maccioni, H J

    1985-01-01

    The content of gangliosides and sialosylglycoproteins was investigated in a coated-vesicle-enriched fraction prepared from bovine brain by the method of Pearse [(1975) J. Mol. Biol. 97, 93-98] and further purified by g.p.c. (glass-permeation chromatography) [Pfeffer & Kelly (1981) J. Cell Biol. 91, 385-391]. From morphological criteria and from the analysis of the polypeptide pattern on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis the coated-vesicle fraction (CV-fraction) appeared more than 95% pure. The ganglioside-NeuAc (N-acetylneuraminate), glycoprotein-NeuAc, phospholipid and cholesterol contents of CV-fraction were compared with those of bovine brain synaptic plasma membranes (SPM). The cholesterol to phospholipid molar ratio was 0.47 +/- 0.07 in CV-fraction and 1.06 +/- 0.08 in SPM. The ganglioside-NeuAc and glycoprotein-NeuAc to phospholipid molar ratios were 0.047 and 0.020 respectively in CV-fraction and 0.039 and 0.016 respectively in SPM. The (Na+ + K+)-dependent ATPase activity sensitive to ouabain (in mumol of Pi/h per nmol of phospholipid) was 1.04 in CV-fraction and 0.63 in SPM; the ratio between this activity and the activity resistant to ouabain was 2 in CV-fraction and 1.4 in SPM. A t.l.c. analysis of the ganglioside fractions showed that most of the ganglioside species present in SPM were present in CV-fraction. In a rat brain coated-vesicle preparation not subjected to g.p.c., the activities [as sugar-radioactivity (c.p.m.) transferred/h per mumol of phospholipid] of the enzymes CMP-NeuAc:sialosyl-lactosylceramide (GM3) sialosyl-, UDP-Gal:N-acetylgalactosaminyl(sialosyl)lactosylceramide (GM2) galactosyl- and UDP-GalNAc:sialosyl-lactosylceramide (GM3) N-acetylgalactosaminyl-transferases, which were considered Golgi-apparatus markers, were about 19, 16 and 10% respectively of those determined in rat brain neuronal perikaryon-enriched fractions. Taken together, the results indicate that most of the major gangliosides are constituents

  15. Rapid and sensitive MRM-based mass spectrometry approach for systematically exploring ganglioside-protein interactions.

    PubMed

    Tian, Ruijun; Jin, Jing; Taylor, Lorne; Larsen, Brett; Quaggin, Susan E; Pawson, Tony

    2013-04-01

    Gangliosides are ubiquitous components of cell membranes. Their interactions with bacterial toxins and membrane-associated proteins (e.g. receptor tyrosine kinases) have important roles in the regulation of multiple cellular functions. Currently, an effective approach for measuring ganglioside-protein interactions especially in a large-scale fashion is largely missing. To this end, we report a facile MS-based approach to explore gangliosides extracted from cells and measure their interactions with protein of interest globally. We optimized a two-step protocol for extracting total gangliosides from cells within 2 h. Easy-to-use magnetic beads conjugated with a protein of interest were used to capture interacting gangliosides. To measure ganglioside-protein interaction on a global scale, we applied a high-sensitive LC-MS system, containing hydrophilic interaction LC separation and multiple reaction monitoring-based MS for ganglioside detection. Sensitivity for ganglioside GM1 is below 100 pg, and the whole analysis can be done in 20 min with isocratic elution. To measure ganglioside interactions with soluble vascular endothelial growth factor receptor 1 (sFlt1), we extracted and readily detected 36 species of gangliosides from perivascular retinal pigment epithelium cells across eight different classes. Twenty-three ganglioside species have significant interactions with sFlt1 as compared with IgG control based on p value cutoff <0.05. These results show that the described method provides a rapid and high-sensitive approach for systematically measuring ganglioside-protein interactions. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Botulinum Neurotoxin Serotype C Associates with Dual Ganglioside Receptors to Facilitate Cell Entry*

    PubMed Central

    Karalewitz, Andrew P.-A.; Fu, Zhuji; Baldwin, Michael R.; Kim, Jung-Ja P.; Barbieri, Joseph T.

    2012-01-01

    Botulinum neurotoxins (BoNTs) cleave SNARE proteins in motor neurons that inhibits synaptic vesicle (SV) exocytosis, resulting in flaccid paralysis. There are seven BoNT serotypes (A–G). In current models, BoNTs initially bind gangliosides on resting neurons and upon SV exocytosis associate with the luminal domains of SV-associated proteins as a second receptor. The entry of BoNT/C is less clear. Characterizing the heavy chain receptor binding domain (HCR), BoNT/C was shown to utilize gangliosides as dual host receptors. Crystallographic and biochemical studies showed that the two ganglioside binding sites, termed GBP2 and Sia-1, were independent and utilized unique mechanisms to bind complex gangliosides. The GBP2 binding site recognized gangliosides that contained a sia5 sialic acid, whereas the Sia-1 binding site recognized gangliosides that contained a sia7 sialic acid and sugars within the backbone of the ganglioside. Utilizing gangliosides that uniquely recognized the GBP2 and Sia-1 binding sites, HCR/C entry into Neuro-2A cells required both functional ganglioside binding sites. HCR/C entered cells differently than the HCR of tetanus toxin, which also utilizes dual gangliosides as host receptors. A point-mutated HCR/C that lacked GBP2 binding potential retained the ability to bind and enter Neuro-2A cells. This showed that ganglioside binding at the Sia-1 site was accessible on the plasma membrane, suggesting that SV exocytosis may not be required to expose BoNT/C receptors. These studies highlight the utility of BoNT HCRs as probes to study the role of gangliosides in neurotransmission. PMID:23027864

  17. Gd3+ spin-lattice relaxation via multi-band conduction electrons in Y(1-x)Gd(x)In3: an electron spin resonance study.

    PubMed

    Cabrera-Baez, M; Iwamoto, W; Magnavita, E T; Osorio-Guillén, J M; Ribeiro, R A; Avila, M A; Rettori, C

    2014-04-30

    Interest in the electronic structure of the intermetallic compound YIn3 has been renewed with the recent discovery of superconductivity at T ∼ 1 K, which may be filamentary in nature. In this work we perform electron spin resonance (ESR) experiments on Gd(3+) doped YIn3 (Y1-xGdxIn3; 0.001 ⪅ x ⩽̸ 0.08), showing that the spin-lattice relaxation of the Gd(3+) ions, due to the exchange interaction between the Gd(3+) localized magnetic moment and the conduction electrons (ce), is processed via the presence of s-, p- and d-type ce at the YIn3 Fermi level. These findings are revealed by the Gd(3+) concentration dependence of the Korringa-like relaxation rate d(ΔH)/dT and g-shift (Δg = g - 1.993), that display bottleneck relaxation behavior for the s-electrons and unbottleneck behavior for the p- and d-electrons. The Korringa-like relaxation rates vary from 22(2) Oe/K for x ⪅ 0.001 to 8(2) Oe/K for x = 0.08 and the g-shift values change, respectively, from a positive Δg = +0.047(10) to a negative Δg = -0.008(4). Analysis in terms of a three-band ce model allows the extraction of the corresponding exchange interaction parameters Jfs, Jfp and Jfd.

  18. Enhanced near-infrared emission in phase and size controlled NaLnF4: Pr3+-Yb3+ (Ln = Gd3+ and Y3+) nanocrystals

    NASA Astrophysics Data System (ADS)

    Ye, Song; Hu, Rongxuan; Wang, Huiyun; Wang, Deping

    2015-01-01

    NaLnF4 (Ln = Y, Gd): Pr3+, Yb3+ nanocrystals were prepared through a facile modified solvothermal method, in which the cubic to hexagonal phase transformation and size evaluation of NaLnF4 nanocrystals could be well controlled by carefully adjusting Gd3+ content. In this system, the infrared emission associated with Yb3+: 2F5/2 → 2F7/2 transition could be obtained under the excitation of Pr3+: 3P0 energy level as a result of efficient energy transfer from Pr3+ to Yb3+. The structural and spectral measurement indicated that the energy transfer efficiency from Pr3+ to Yb3+ firstly increased with the increase of Gd3+ content due to the formation of a higher percentage of hexagonal phase NaLnF4 in the final production, and then decreased with further increase in Gd3+ content due to the expansion of NaLnF4 unit-cell volume. However, a monotonous increase in Yb3+ infrared emission intensity could be observed with the increasing of Gd3+ content until the radiative emission was suppressed by the nonradiative transition originating from the surface defects in smaller NaLnF4 nanocrystals.

  19. Synthesis and luminescent properties of Gd3Ga2Al3O12 phosphors doped with Eu3+ or Ce3+

    NASA Astrophysics Data System (ADS)

    Oh, M. J.; Kim, H. J.

    2016-09-01

    Eu3+-or Ce3+-doped gadolinium gallium aluminum garnet (GGAG), Gd3Ga2Al3O12, phosphors are fabricated using solid-state reactions with Gd2O3, Ga2O3, Al2O3, CeO2 and Eu2O3 powders. The Eu3+-or Ce3+-doped Gd3Ga2Al3O12 phosphors are sintered at 1300 °C or 1600 °C for 5 hours by using an electric furnace under normal atmosphere. X-ray diffraction and field-emission scanning electron microscopy studies are carried out in order to analyze the physical properties of these materials, and their luminescence properties are also measured by using UV and X-ray sources. The Eu3+-or Ce3+-doped Gd3Ga2Al3O12 phosphors show higher light yields in comparison to commercial phosphors such as Gd2O2S:Tb (gadox). This indicates that Gd3Ga2Al3O12:Eu3+ phosphors are promising materials for use in X-ray imaging and dose monitoring at proton beamlines.

  20. Differential Distribution of Major Brain Gangliosides in the Adult Mouse Central Nervous System

    PubMed Central

    Vajn, Katarina; Viljetić, Barbara; Degmečić, Ivan Večeslav; Schnaar, Ronald L.; Heffer, Marija

    2013-01-01

    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 biochemical and immunohistochemical 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-associated 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. PMID:24098718

  1. Anti-ganglioside antibodies are removed from circulation in mice by neuronal endocytosis

    PubMed Central

    Cunningham, Madeleine E.; McGonigal, Rhona; Meehan, Gavin R.; Barrie, Jennifer A.; Yao, Denggao; Halstead, Susan K.

    2016-01-01

    See van Doorn and Jacobs (doi:10.1093/brain/aww078) for a scientific commentary on this article.   In axonal forms of Guillain-Barré syndrome, anti-ganglioside antibodies bind gangliosides on nerve surfaces, thereby causing injury through complement activation and immune cell recruitment. Why some nerve regions are more vulnerable than others is unknown. One reason may be that neuronal membranes with high endocytic activity, including nerve terminals involved in neurotransmitter recycling, are able to endocytose anti-ganglioside antibodies from the cell surface so rapidly that antibody-mediated injury is attenuated. Herein we investigated whether endocytic clearance of anti-ganglioside antibodies by nerve terminals might also be of sufficient magnitude to deplete circulating antibody levels. Remarkably, systemically delivered anti-ganglioside antibody in mice was so avidly cleared from the circulation by endocytosis at ganglioside-expressing plasma membranes that it was rapidly rendered undetectable in serum. A major component of the clearance occurred at motor nerve terminals of neuromuscular junctions, from where anti-ganglioside antibody was retrogradely transported to the motor neuron cell body in the spinal cord, recycled to the plasma membrane, and secreted into the surrounding spinal cord. Uptake at the neuromuscular junction represents a major unexpected pathway by which pathogenic anti-ganglioside antibodies, and potentially other ganglioside binding proteins, are cleared from the systemic circulation and also covertly delivered to the central nervous system. PMID:27017187

  2. Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa.

    PubMed

    Gavella, Mirjana; Lipovac, Vaskresenija

    2013-05-01

    This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species (ROS)-mediated damage. The antioxidative efficacy of exogenous gangliosides in protecting different cells encouraged us to examine their ability to protect human spermatozoa. Gangliosides are sialic acid-containing glycosphingolipids with strong amphiphilic character due to the bulky headgroup made of several sugar rings with sialic acid residues and the double-tailed hydrophobic lipid moiety. The amphiphilicity of gangliosides allows them to exist as micelles in aqueous media when they are present at a concentration above their critical micellar concentration. The protective effect of ganglioside micelles on spermatozoa is believed to stem from their ability to scavenge free radicals and prevent their damaging effects. In our study, we particularly focused our attention on the protective effect of ganglioside micelles on DNA in human spermatozoa exposed to cryopreservation. The results indicate that ganglioside micelles can modulate the hydrophobic properties of the sperm membrane to increase tolerance to DNA fragmentation, thus protecting the DNA from cryopreservation-induced damage. Further actions of ganglioside micelles, which were documented by biochemical and biophysical studies, included (i) the modulation of superoxide anion generation by increasing the diffusion barrier for membrane events responsible for signal translocation to the interior of the cell; (ii) the inhibition of iron-catalysed hydroxyl radical formation due to the iron chelation potential of gangliosides; and (iii) inhibition of hydrogen peroxide diffusion across the sperm membrane.

  3. Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa

    PubMed Central

    Gavella, Mirjana; Lipovac, Vaskresenija

    2013-01-01

    This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species (ROS)-mediated damage. The antioxidative efficacy of exogenous gangliosides in protecting different cells encouraged us to examine their ability to protect human spermatozoa. Gangliosides are sialic acid-containing glycosphingolipids with strong amphiphilic character due to the bulky headgroup made of several sugar rings with sialic acid residues and the double-tailed hydrophobic lipid moiety. The amphiphilicity of gangliosides allows them to exist as micelles in aqueous media when they are present at a concentration above their critical micellar concentration. The protective effect of ganglioside micelles on spermatozoa is believed to stem from their ability to scavenge free radicals and prevent their damaging effects. In our study, we particularly focused our attention on the protective effect of ganglioside micelles on DNA in human spermatozoa exposed to cryopreservation. The results indicate that ganglioside micelles can modulate the hydrophobic properties of the sperm membrane to increase tolerance to DNA fragmentation, thus protecting the DNA from cryopreservation-induced damage. Further actions of ganglioside micelles, which were documented by biochemical and biophysical studies, included (i) the modulation of superoxide anion generation by increasing the diffusion barrier for membrane events responsible for signal translocation to the interior of the cell; (ii) the inhibition of iron-catalysed hydroxyl radical formation due to the iron chelation potential of gangliosides; and (iii) inhibition of hydrogen peroxide diffusion across the sperm membrane. PMID:23503425

  4. Alteration of ganglioside synthesis by GM3 synthase knockout in murine embryonic fibroblasts.

    PubMed

    Shevchuk, Nikolai A; Hathout, Yetrib; Epifano, Olga; Su, Yan; Liu, Yihui; Sutherland, Margaret; Ladisch, Stephan

    2007-09-01

    To probe the functions of membrane gangliosides, the availability of ganglioside-depleted cells would be a valuable resource. To attempt to identify a useful genetic model of ganglioside depletion, we assessed ganglioside metabolism in murine GM3 synthase (GM3S)-/- knockout primary embryonic fibroblasts (MEF), because normal fibroblast gangliosides (GM3, GM2, GM1, and GD1a), all downstream products of GM3S, should be absent. We found that heterozygote MEF (GM3S+/-) did have a 36% reduced content of qualitatively normal gangliosides (7.0+/-0.8 nmol LBSA/mg cell protein; control: 11+/-1.6 nmol). However, two unexpected findings characterized the homozygous (GM3-/-) MEF. Despite complete knockout of GM3S, (i) GM3-/- MEF retained substantial ganglioside content (21% of normal or 2.3+/-1.1 nmol) and (ii) these gangliosides were entirely different from those of wild type MEF by HPTLC. Mass spectrometry identified them as GM1b, GalNAc-GM1b, and GD1alpha, containing both N-acetyl and N-glycolylneuraminic acid and diverse ceramide structures. All are products of the 0 pathway of ganglioside synthesis, not normally expressed in fibroblasts. The results suggest that complete, but not partial, inhibition of GM3 synthesis results in robust activation of an alternate pathway that may compensate for the complete absence of the products of GM3S.

  5. Anti-ganglioside antibodies are removed from circulation in mice by neuronal endocytosis.

    PubMed

    Cunningham, Madeleine E; McGonigal, Rhona; Meehan, Gavin R; Barrie, Jennifer A; Yao, Denggao; Halstead, Susan K; Willison, Hugh J

    2016-06-01

    SEE VAN DOORN AND JACOBS DOI101093/BRAIN/AWW078 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE  : In axonal forms of Guillain-Barré syndrome, anti-ganglioside antibodies bind gangliosides on nerve surfaces, thereby causing injury through complement activation and immune cell recruitment. Why some nerve regions are more vulnerable than others is unknown. One reason may be that neuronal membranes with high endocytic activity, including nerve terminals involved in neurotransmitter recycling, are able to endocytose anti-ganglioside antibodies from the cell surface so rapidly that antibody-mediated injury is attenuated. Herein we investigated whether endocytic clearance of anti-ganglioside antibodies by nerve terminals might also be of sufficient magnitude to deplete circulating antibody levels. Remarkably, systemically delivered anti-ganglioside antibody in mice was so avidly cleared from the circulation by endocytosis at ganglioside-expressing plasma membranes that it was rapidly rendered undetectable in serum. A major component of the clearance occurred at motor nerve terminals of neuromuscular junctions, from where anti-ganglioside antibody was retrogradely transported to the motor neuron cell body in the spinal cord, recycled to the plasma membrane, and secreted into the surrounding spinal cord. Uptake at the neuromuscular junction represents a major unexpected pathway by which pathogenic anti-ganglioside antibodies, and potentially other ganglioside binding proteins, are cleared from the systemic circulation and also covertly delivered to the central nervous system. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

  6. Brain gangliosides in hibernating dormice (Glis glis) and cold-exposed laboratory mice.

    PubMed

    Mühleisen, M; Hilbig, R; Rahmann, H

    1984-01-01

    The concentration of proteins, sialo-glycoproteins and gangliosides and the ganglioside composition of 8 brain regions from normothermic and hibernating fat dormice (Glis glis) and from laboratory mice being acclimated to 6, 22 and 28 degrees C were investigated. During hibernation the concentration of sialo-glycoproteins and gangliosides decreased significantly in brain of dormice; the protein content remained uninfluenced. Cold-exposure of laboratory mice yielded generally a slightly decreased sialo-glycoprotein concentration in brain; the data on ganglioside concentration in the CNS were not uniform. The ganglioside composition of brain of laboratory mice being kept at different environmental temperatures did not show any alterations. The brain gangliosides of hibernating dormice in contrast to their normothermic counterparts are more polar (higher amount of GTlb and GQlb.). Most striking is the complete absence of a distinct ganglioside fraction (O-acetylated-GTlb) during hibernation. Brain gangliosides of normothermic dormice were found to be more sensitive against neuraminidase treatment than those of hibernating animals. The results are discussed with regard to modulatory functions of neuronal gangliosides for the process of synaptic transmission during seasonal adaptation.

  7. Effect of Ga(3+) and Gd(3+) ions substitution on the structural and optical properties of Ce(3+) -doped yttrium aluminium garnet phosphor nanopowders.

    PubMed

    Wako, A H; Dejene, F B; Swart, H C

    2016-11-01

    The structural and optical properties of commercially obtained Y3 Al5 O12 :Ce(3)(+) phosphor were investigated by replacing Al(3)(+) with Ga(3)(+) and Y(3)(+) with Gd(3)(+) in the Y3 Al5 O12 :Ce(3)(+) structure to form Y3 (Al,Ga)5 O12 :Ce(3)(+) and (Y,Gd)3 Al5 O12 :Ce(3)(+) . X-Ray diffraction (XRD) results showed slight 2-theta peak shifts to lower angles when Ga(3)(+) was used and to higher angles when Gd(3)(+) was used, with respect to peaks from Y3 Al5 O12 :Ce(3)(+) and JCPDS card no. 73-1370. This could be attributed to induced crystal-field effects due to the different ionic sizes of Ga(3)(+) and Gd(3)(+) compared with Al(3)(+) and Y(3)(+) . The photoluminescence (PL) spectra showed broad excitation from 350 to 550 nm with a maximum at 472 nm, and broad emission bands from 500 to 650 nm, centred at 578 nm for Y3 Al5 O12 :Ce(3)(+) arising from the 5d → 4f transition of Ce(3)(+) . PL revealed a blue shift for Ga(3)(+) substitution and a red shift for Gd(3)(+) substitution. UV-Vis showed two absorption peaks at 357 and 457 nm for Y3 Al5 O12 :Ce(3)(+) , with peaks shifting to 432 nm for Ga(3)(+) and 460 nm for Gd(3)(+) substitutions. Changes in the trap levels or in the depth and number of traps due to Ce(3)(+) were analysed using thermoluminescence (TL) spectroscopy. This revealed the existence of shallow and deep traps. It was observed that Ga(3)(+) substitution contributes to the shallowest traps at 74 °C and fewer deep traps at 163 °C, followed by Gd(3)(+) with shallow traps at 87 °C and deep traps at 146 °C. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Photoluminescence properties of phosphors based on Lu3+-stabilized Gd3Al5O12:Tb3+/Ce3+ garnet solid solutions

    NASA Astrophysics Data System (ADS)

    Li, Jinkai; Li, Ji-Guang; Li, Xiaodong; Sun, Xudong

    2016-12-01

    The Gd3Al5O12:Tb/Ce (GdAG:Tb/Ce) garnet solutions effectively stabilized by Lu3+ have been achieved by calcining their precursor at 1300 °C. Detailed characterizations are given to the materials in terms of XRD, FE-SEM, BET, PL/PLE, and fluorescence decay analysis. The occurrence of Gd3+ and Tb3+ transitions from the photoluminescence excitation spectrum monitoring the Ce3+ yellow emission strongly confirmed the efficient Gd3+ → Ce3+ and Tb3+ → Ce3+ energy transfer. The [(Gd0.8Lu0.2)0.99-xCe0.01Tbx]AG (x = 0-0.1) phosphors with good dispersion and uniform particle size exhibit various luminescent properties under different excitation wavelength of 275, 338, and 457 nm, respectively. The photoluminescence comparison indicated that owing to the Gd3+ → Ce3+ and Tb3+ → Ce3+ energy transfer, the best luminescent phosphor [(Gd0.8Lu0.2)0.89Ce0.01 Tb0.1]AG is almost identical to the well-known YAG:Ce, higher than LuAG:Ce in emission intensity, and has a substantially red-shifted emission band that is desired for warm-white lighting. The Tb3+ → Ce3+ energy transfer was suggested to be electric multipolar interactions, and the processes of energy migration among the optically active Gd3+, Tb3+, and Ce3+ ions were discussed in detail. Fluorescence decay analysis found the lifetime for the Ce3+ emission hardly changes with the Tb3+ incorporation. The [(Gd0.8Lu0.2)0.99-xCe0.01Tbx]AG garnets developed in this work may serve as a new type of phosphor that hopefully meets the requirements of various lighting, optical display, and scintillation applications.

  9. Structural and optical properties of Eu3+/Gd3+ ions in silica xerogels and powders obtained by sol-gel method

    NASA Astrophysics Data System (ADS)

    Pawlik, Natalia; Szpikowska-Sroka, Barbara; Swinarew, Andrzej S.; Łężniak, Marta; Pisarski, Wojciech A.

    2016-12-01

    The xerogels and sol-gel powders with different quantitative composition have been studied based on excitation and emission measurements as well as luminescence decay analysis. The structure of prepared silica sol-gel materials was examined using FT-IR spectroscopy technique. The photoluminescence spectra of Eu3+ ions were registered upon two different excitation wavelengths related to direct excitation of Eu3+ ions (λexc = 393 nm) and indirect excitation through energy transfer process from Gd3+ to Eu3+ (λexc = 273 nm). Upon direct excitation of Eu3+ (7F0 → 5L6 transition) the characteristic emission bands assigned to the 5D0 → 7FJ(0-4) electronic transitions were observed. Also, it was found that enhanced luminescence of Eu3+ is a result of change the excitation parameter through energy transfer phenomenon (8S7/2 → 6IJ transition of Gd3+) and occurred in both xerogels and powder samples. In this way, a UV photon absorbed by Gd3+ is converted into visible light emitted by Eu3+ ions. Obtained results clearly indicated that high concentration of Gd3+ ions in powders led to particularly strong enhance the emission in red spectral range and allowed for more than 12-times prolongation of luminescence lifetime for the 5D0 excited state of Eu3+ compared to silica xerogel samples. The values of energy transfer efficiency were also estimated based on luminescence decay times of the 6P7/2 state of Gd3+ ions.

  10. Zika virus and neurologic autoimmunity: the putative role of gangliosides.

    PubMed

    Anaya, Juan-Manuel; Ramirez-Santana, Carolina; Salgado-Castaneda, Ignacio; Chang, Christopher; Ansari, Aftab; Gershwin, M Eric

    2016-03-21

    An increasing number of severe neurological complications associated with Zika virus (ZIKV), chiefly Guillain-Barré syndrome (GBS) and primary microcephaly, have led the World Health Organization to declare a global health emergency. Molecular mimicry between glycolipids and surface molecules of infectious agents explain most of the cases of GBS preceded by infection, while a direct toxicity of ZIKV on neural cells has been raised as the main mechanism by which ZIKV induces microcephaly. Gangliosides are crucial in brain development, and their expression correlates with neurogenesis, synaptogenesis, synaptic transmission, and cell proliferation. Targeting the autoimmune response to gangliosides may represent an underexploited opportunity to examine the increased incidence of neurological complications related to ZIKV infection.

  11. Impairment of neuropsychological behaviors in ganglioside GM3-knockout mice.

    PubMed

    Niimi, Kimie; Nishioka, Chieko; Miyamoto, Tomomi; Takahashi, Eiki; Miyoshi, Ichiro; Itakura, Chitoshi; Yamashita, Tadashi

    2011-03-25

    The ganglioside GM3 synthase (SAT-I), encoded by a single-copy gene, is a primary glycosyltransferase for the synthesis of complex gangliosides. Although its expression is tightly controlled during early embryo development and postnatal development and maturation in the brain, the physiological role of ganglioside GM3 in the regulation of neuronal functions has not been elucidated. In the present study, we examined motor activity, cognitive and emotional behaviors, and drug administration in juvenile GM3-knockout (GM3-KO) mice. GM3-KO male and female mice showed hyperactivity in the motor activity test, Y-maze test, and elevated plus maze test. In the Y-maze test, there was significantly less spontaneous alternation behavior in GM3-KO male mice than in wild-type mice. In the elevated plus maze test, the amount of time spent on the open arms by GM3-KO male mice was significantly higher than that of sex-matched wild-type mice. In contrast, there was no significant difference between GM3-KO and wild-type female mice in these tests. Thus, juvenile GM3-KO mice show gender-specific phenotypes resembling attention-deficit hyperactivity disorder (ADHD), namely hyperactivity, reduced attention, and increased impulsive behaviors. However, administration of methylphenidate hydrochloride (MPH) did not ameliorate hyperactivity in either male or female GM3-KO mice. Although these data demonstrate the involvement of ganglioside GM3 in ADHD and the ineffectiveness of MPH, the first-choice psychostimulant for ADHD medication, our studies indicate that juvenile GM3-KO mice are a useful tool for neuropsychological studies. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Gangliosides During Tumor Progression in Patients With Prostate Cancer

    DTIC Science & Technology

    2004-07-01

    LSCFM, Thiruverkadu S. Saravanan, Ph.D. and Meena Verma, M.B., B.S., for other technical support. 15 References 1. P. M . Gullino , Prostaglandins and...121-135. 3. G. Alessandri, P. Cornaglia-Ferraris, P. M . Gullino , Angiogenic and angiostatic microenvironment in tumors-role of gangliosides. Acta...Wiegandt (Ed), Glycolipids, Elsevier, Amsterdam, 1985, pp. 199-260. 11. M . L . Freimer, K. McIntosh, R. A. Adams, C. R. Alving, D. B. Drachman

  13. Synthesis of visible light active Gd3+-substituted ZnFe2O4 nanoparticles for photocatalytic and antibacterial activities

    NASA Astrophysics Data System (ADS)

    Patil, S. B.; Bhojya Naik, H. S.; Nagaraju, G.; Viswanath, R.; Rashmi, S. K.

    2017-08-01

    In the present analysis, we study the assembly of a low-cost and visible light active ZnFe2-xGdxO4 ( x = 0 , 0.3, 0.5 and 0.7) nanoparticles (NPs) photocatalyst. The synthesized samples were characterized by several physicochemical techniques, such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), UV-Visible absorption spectroscopy (UV-Vis), scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HRTEM). The phase transition from cubic to orthorhombic was confirmed by XRD patterns. The increase in the concentration of Gd3+ substitution in ZnFe2O4 NPs enhances the redshift of absorption in the visible region of UV-Vis absorption spectra and reduces the band gap. In the photo-Fenton-type reaction, the gadolinium-substituted zinc ferrite (ZGF) NPs exhibit a significant catalytic activity for the degradation of methylene blue (99% in 90 minutes) under visible light (500W xenon lamp) with respect to bare samples (95% in 240 minutes) and they also show an excellent reusability nature. These materials were also screened for antibacterial activity against Gram-negative bacteria strains ( Pseudomonas aeruginosa and Escherichia coli).

  14. Performance test of the Gd3Al2Ga3O12 (GAGG) scintillator for the nuclear astrophysics experiment

    NASA Astrophysics Data System (ADS)

    Koshikawa, Ami; Adachi, Satoshi; Furuno, Tatsuya; Kawabata, Takahiro; Tsumura, Miho; Kurosawa, Shunsuke

    2014-09-01

    The γ-decay widths of the excited states in 12C are very important quantities to understand the nucleosynthesis in the universe, but the γ-decay widths for the 31- and 22+ states in 12C have never been measured. To determine the γ-decay widths of the 31- state, we propose to measure the 1H(<12C, 12C*p) reaction under the inverse kinematics condition. The energies and emission angles of the scattered 12C and the recoil proton will be measured by the magnetic spectrometer Grand Raiden and the Si-CsI counter telescope, respectively. We carried out a test experiment at RCNP, Osaka and found that the energy resolution of the CsI detector is poorer than expected due to the high counting rate. To solve the pile-up problem in the recoil proton detector, we have started the performance test of the Ce-doped Gd3Al2Ga3O12 (GAGG) scintillator. The Ce-doped GAGG was recently developed and it has better light output and shorter scintillation decay time than CsI. In the present talk, the results of the performance test of the Ce-doped GAGG scintillator will be reported.

  15. Temperature and pressure dependence of the optical properties of Cr3+-doped Gd3Ga5O12 nanoparticles.

    PubMed

    Martín-Rodríguez, R; Valiente, R; Rodríguez, F; Bettinelli, M

    2011-07-01

    Since the crystal-field strength at the Cr(3+) site is very close to the excited-state crossover (ESCO), this work investigates the optical properties of Cr(3+)-doped Gd(3)Ga(5)O(12) (GGG) nanoparticles as a function of temperature and pressure in order to establish the effect of the ESCO on the optical behaviour of nanocrystalline GGG. Luminescence, time-resolved emission and lifetime measurements have been performed on GGG:0.5% Cr(3+) nanoparticles in the 25-300 K temperature range, as well as under hydrostatic pressure up to 20 GPa. We show how low temperature and high pressure progressively transforms Cr(3+)(4)T(2) --> (4)A(2) broadband emission into a ruby-like (2)E --> (4)A(2) luminescence. This behaviour together with the lifetime dependence on pressure and temperature are explained on the basis of the spin-orbit interaction between the (4)T(2) and (2)E states of Cr(3+).

  16. Temperature and pressure dependence of the optical properties of Cr3 + -doped Gd3Ga5O12 nanoparticles

    NASA Astrophysics Data System (ADS)

    Martín-Rodríguez, R.; Valiente, R.; Rodríguez, F.; Bettinelli, M.

    2011-07-01

    Since the crystal-field strength at the Cr3 + site is very close to the excited-state crossover (ESCO), this work investigates the optical properties of Cr3 + -doped Gd3Ga5O12 (GGG) nanoparticles as a function of temperature and pressure in order to establish the effect of the ESCO on the optical behaviour of nanocrystalline GGG. Luminescence, time-resolved emission and lifetime measurements have been performed on GGG:0.5% Cr3 + nanoparticles in the 25-300 K temperature range, as well as under hydrostatic pressure up to 20 GPa. We show how low temperature and high pressure progressively transforms {Cr}^{3+}~^{4} {T}_{2} \\to {}^{4} {A}_{2} broadband emission into a ruby-like ^{2} {E} \\to {}^{4} {A}_{2} luminescence. This behaviour together with the lifetime dependence on pressure and temperature are explained on the basis of the spin-orbit interaction between the 4T2 and 2E states of Cr3 + .

  17. A comparison of the ganglioside distributions of fat tissues in various animals by two-dimensional thin layer chromatography.

    PubMed

    Ohashi, M

    1979-01-01

    The ganglioside distributions of various fat tissues from human, rabbit, rat, mouse, chicken and frog were compared with pig adipose gangliosides by two-dimensional thin layer chromatography. It was found that there is a remarkable species variation in ganglioside distribution, especially in the composition and relative concentration of complex gangliosides. Differing from pig adipose tissues, those of human, rabbit, rat, mouse, chicken, but not frog, contained GM3 as a most abundant ganglioside. The data for human, rabbit and chicken indicated a simple distribution of only NeuAc-type gangliosides, while those for rat and mouse indicated a rather complicated pattern containing both NeuAc- and NeuGc-type gangliosides. The ganglioside pattern of the frog fat body differed markedly from those of mammalian fat tissues because of the presence of three different, unusual monosialosylgangliosides as major components. In other respects, a substantial amount of disialosylgangliosides was commonly found in all animal fat tissues.

  18. Botulinum neurotoxin serotype C associates with dual ganglioside receptors to facilitate cell entry.

    PubMed

    Karalewitz, Andrew P-A; Fu, Zhuji; Baldwin, Michael R; Kim, Jung-Ja P; Barbieri, Joseph T

    2012-11-23

    How botulinum neurotoxin serotype C (BoNT/C) enters neurons is unclear. BoNT/C utilizes dual gangliosides as host cell receptors. BoNT/C accesses gangliosides on the plasma membrane. Plasma membrane accessibility of the dual ganglioside receptors suggests synaptic vesicle exocytosis may not be necessary to expose BoNT/C receptors. Botulinum neurotoxins (BoNTs) cleave SNARE proteins in motor neurons that inhibits synaptic vesicle (SV) exocytosis, resulting in flaccid paralysis. There are seven BoNT serotypes (A-G). In current models, BoNTs initially bind gangliosides on resting neurons and upon SV exocytosis associate with the luminal domains of SV-associated proteins as a second receptor. The entry of BoNT/C is less clear. Characterizing the heavy chain receptor binding domain (HCR), BoNT/C was shown to utilize gangliosides as dual host receptors. Crystallographic and biochemical studies showed that the two ganglioside binding sites, termed GBP2 and Sia-1, were independent and utilized unique mechanisms to bind complex gangliosides. The GBP2 binding site recognized gangliosides that contained a sia5 sialic acid, whereas the Sia-1 binding site recognized gangliosides that contained a sia7 sialic acid and sugars within the backbone of the ganglioside. Utilizing gangliosides that uniquely recognized the GBP2 and Sia-1 binding sites, HCR/C entry into Neuro-2A cells required both functional ganglioside binding sites. HCR/C entered cells differently than the HCR of tetanus toxin, which also utilizes dual gangliosides as host receptors. A point-mutated HCR/C that lacked GBP2 binding potential retained the ability to bind and enter Neuro-2A cells. This showed that ganglioside binding at the Sia-1 site was accessible on the plasma membrane, suggesting that SV exocytosis may not be required to expose BoNT/C receptors. These studies highlight the utility of BoNT HCRs as probes to study the role of gangliosides in neurotransmission.

  19. Novel ganglioside-mediated entry of botulinum neurotoxin serotype D into neurons.

    PubMed

    Kroken, Abby R; Karalewitz, Andrew P-A; Fu, Zhuji; Kim, Jung-Ja P; Barbieri, Joseph T

    2011-07-29

    Botulinum Neurotoxins (BoNTs) are organized into seven serotypes, A-G. Although several BoNT serotypes enter neurons through synaptic vesicle cycling utilizing dual receptors (a ganglioside and a synaptic vesicle-associated protein), the entry pathway of BoNT/D is less well understood. Although BoNT/D entry is ganglioside-dependent, alignment and structural studies show that BoNT/D lacks key residues within a conserved ganglioside binding pocket that are present in BoNT serotypes A, B, E, F, and G, which indicate that BoNT/D-ganglioside interactions may be unique. In this study BoNT/D is shown to have a unique association with ganglioside relative to the other BoNT serotypes, utilizing a ganglioside binding loop (GBL, residues Tyr-1235-Ala-1245) within the receptor binding domain of BoNT/D (HCR/D) via b-series gangliosides, including GT1b, GD1b, and GD2. HCR/D bound gangliosides and entered neurons dependent upon the aromatic ring of Phe-1240 within the GBL. This is the first BoNT-ganglioside interaction that is mediated by a phenylalanine. In contrast, Trp-1238, located near the N terminus of the ganglioside binding loop, was mostly solvent-inaccessible and appeared to contribute to maintaining the loop structure. BoNT/D entry and intoxication were enhanced by membrane depolarization via synaptic vesicle cycling, where HCR/D colocalized with synaptophysin, a synaptic vesicle marker, but immunoprecipitation experiments did not detect direct association with synaptic vesicle protein 2. Thus, BoNT/D utilizes unique associations with gangliosides and synaptic vesicles to enter neurons, which may facilitate new neurotoxin therapies.

  20. Novel Ganglioside-mediated Entry of Botulinum Neurotoxin Serotype D into Neurons

    SciTech Connect

    Kroken, Abby R.; Karalewitz, Andrew P.-A.; Fu, Zhuji; Kim, Jung-Ja P.; Barbieri, Joseph T.

    2012-02-07

    Botulinum Neurotoxins (BoNTs) are organized into seven serotypes, A-G. Although several BoNT serotypes enter neurons through synaptic vesicle cycling utilizing dual receptors (a ganglioside and a synaptic vesicle-associated protein), the entry pathway of BoNT/D is less well understood. Although BoNT/D entry is ganglioside-dependent, alignment and structural studies show that BoNT/D lacks key residues within a conserved ganglioside binding pocket that are present in BoNT serotypes A, B, E, F, and G, which indicate that BoNT/D-ganglioside interactions may be unique. In this study BoNT/D is shown to have a unique association with ganglioside relative to the other BoNT serotypes, utilizing a ganglioside binding loop (GBL, residues Tyr-1235-Ala-1245) within the receptor binding domain of BoNT/D (HCR/D) via b-series gangliosides, including GT1b, GD1b, and GD2. HCR/D bound gangliosides and entered neurons dependent upon the aromatic ring of Phe-1240 within the GBL. This is the first BoNT-ganglioside interaction that is mediated by a phenylalanine. In contrast, Trp-1238, located near the N terminus of the ganglioside binding loop, was mostly solvent-inaccessible and appeared to contribute to maintaining the loop structure. BoNT/D entry and intoxication were enhanced by membrane depolarization via synaptic vesicle cycling, where HCR/D colocalized with synaptophysin, a synaptic vesicle marker, but immunoprecipitation experiments did not detect direct association with synaptic vesicle protein 2. Thus, BoNT/D utilizes unique associations with gangliosides and synaptic vesicles to enter neurons, which may facilitate new neurotoxin therapies.

  1. GM1 Ganglioside Treatment Facilitates Behavioral Recovery from Bilateral Brain Damage

    NASA Astrophysics Data System (ADS)

    Sabel, Bernhard A.; Slavin, Mary D.; Stein, Donald G.

    1984-07-01

    Adult rats with bilateral lesions of the caudate nucleus were treated with GM1 ganglioside. Although animals injected with a control solution were severely impaired in their ability to learn a complex spatial task, those treated with ganglioside were able to learn spatial reversals.

  2. Gangliosides drive the tumor infiltration and function of myeloid-derived suppressor cells.

    PubMed

    Wondimu, Assefa; Liu, Yihui; Su, Yan; Bobb, Daniel; Ma, Jennifer S Y; Chakrabarti, Lina; Radoja, Saša; Ladisch, Stephan

    2014-10-01

    Although it is now widely appreciated that antitumor immunity is critical to impede tumor growth and progression, there remain significant gaps in knowledge about the mechanisms used by tumors to escape immune control. In tumor cells, we hypothesized that one mechanism of immune escape used by tumors involves the synthesis and extracellular shedding of gangliosides, a class of biologically active cell surface glycosphingolipids with known immunosuppressive properties. In this study, we report that tumor cells engineered to be ganglioside deficient exhibit impaired tumorigenicity, supporting a link between ganglioside-dependent immune escape and tumor outgrowth. Notably, we documented a dramatic reduction in the numbers and function of tumor-infiltrating myeloid-derived suppressor cells (MDSC) in ganglioside-deficient tumors, in contrast with the large MDSC infiltrates seen in ganglioside-rich littermate control tumors. Transient ganglioside reconstitution of the tumor cell inoculum was sufficient to increase MDSC infiltration, supporting a direct connection between ganglioside production by tumor cells and the recruitment of immunosuppressive MDSC into the tumor microenvironment. Our results reveal a novel mechanism of immune escape that supports tumor growth, with broad implications given that many human tumors produce and shed high levels of gangliosides. ©2014 American Association for Cancer Research.

  3. Gangliosides drive the tumor infiltration and function of myeloid-derived suppressor cells

    PubMed Central

    Wondimu, Assefa; Liu, Yihui; Yan, Su; Bobb, Daniel; Ma, Jennifer S.Y.; Chakrabarti, Lina; Radoja, Saša; Ladisch, Stephan

    2014-01-01

    While it is now widely appreciated that anti-tumor immunity is critical to impede tumor growth and progression, there remain significant gaps in knowledge about the mechanisms used by tumors to escape immune control. In tumor cells, we hypothesized that one mechanism of immune escape used by tumors involves the synthesis and extracellular shedding of gangliosides, a class of biologically active cell surface glycosphingolipids with known immunosuppressive properties. In this study, we report that tumor cells engineered to be ganglioside-deficient exhibit impaired tumorigenicity, supporting a link between ganglioside-dependent immune escape and tumor outgrowth. Notably, we documented a dramatic reduction in the numbers and function of tumor-infiltrating myeloid-derived suppressor cells (MDSC) in ganglioside-deficient tumors, in contrast to the large MDSC infiltrates seen in ganglioside-rich littermate control tumors. Transient ganglioside reconstitution of the tumor cell inoculum was sufficient to increase MDSC infiltration, supporting a direct connection between ganglioside production by tumor cells and the recruitment of immunosuppressive MDSC into the tumor microenvironment. Our results reveal a novel mechanism of immune escape that supports tumor growth, with broad implications given that many human tumors produce and shed high levels of gangliosides. PMID:25115301

  4. Gd3+ and Calcium Sensitive, Sodium Leak Currents Are Features of Weak Membrane-Glass Seals in Patch Clamp Recordings

    PubMed Central

    Chemin, Jean; Monteil, Arnaud; Spafford, J. David

    2014-01-01

    The properties of leaky patch currents in whole cell recording of HEK-293T cells were examined as a means to separate these control currents from expressed sodium and calcium leak channel currents from snail NALCN leak channels possessing both sodium (EKEE) and calcium (EEEE) selectivity filters. Leak currents were generated by the weakening of gigaohm patch seals by artificial membrane rupture using the ZAP function on the patch clamp amplifier. Surprisingly, we found that leak currents generated from the weakened membrane/glass seal can be surprisingly stable and exhibit behavior that is consistent with a sodium leak current derived from an expressible channel. Leaky patch currents differing by 10 fold in size were similarly reduced in size when external sodium ions were replaced with the large monovalent ion NMDG+. Leaky patch currents increased when external Ca2+ (1.2 mM) was lowered to 0.1 mM and were inhibited (>40% to >90%) with 10 µM Gd3+, 100 µM La3+, 1 mM Co2+ or 1 mM Cd2+. Leaky patch currents were relatively insensitive (<30%) to 1 mM Ni2+ and exhibited a variable amount of block with 1 mM verapamil and were insensitive to 100 µM mibefradil or 100 µM nifedipine. We hypothesize that the rapid changes in leak current size in response to changing external cations or drugs relates to their influences on the membrane seal adherence and the electro-osmotic flow of mobile cations channeling in crevices of a particular pore size in the interface between the negatively charged patch electrode and the lipid membrane. Observed sodium leak conductance currents in weak patch seals are reproducible between the electrode glass interface with cell membranes, artificial lipid or Sylgard rubber. PMID:24945283

  5. Magnetic behavior of Gd3Ru4Al12, a layered compound with distorted kagomé net

    NASA Astrophysics Data System (ADS)

    Chandragiri, Venkatesh; Iyer, Kartik K.; Sampathkumaran, E. V.

    2016-07-01

    The magnetic behavior of the compound, Gd3Ru4Al12, which was reported about two decades ago to crystallize in a hexagonal structure (space group P63/mmc), has not been investigated in the past literature despite interesting structural features (that is, magnetic layers and triangular as well as kagomé-lattice features favoring frustrated magnetism) characterizing this compound. We report here the results of studies of magnetization, heat capacity and magnetoresistance in the temperature range T  =  1.8-300 K. The results establish that there is a long-range magnetic order of antiferromagnetic type below (T N  =) 18.5 K, despite a much larger value (~80 K) of paramagnetic Curie temperature with a positive sign characteristic of ferromagnetic interaction. We attribute this to geometric frustration. The most interesting finding is that there is an additional magnetic anomaly below ~55 K before the onset of long-range order in the magnetic susceptibility data. Concurrent with this observation, the sign of isothermal change in entropy, ΔS  =  S(0)  -  S(H), where H is the externally applied magnetic field, remains positive above T N, with a broad peak. This observation indicates the presence of ferromagnetic clusters before the onset of long-range magnetic order. Thus, this compound may serve as an example of a situation in which magnetic frustration due to geometrical reasons faces competition from such magnetic precursor effects. There is also a reversal of the sign of  -ΔS in the curves for lower final fields (H  <  30 kOe) on entering the magnetically ordered state consistent with the entrance to an antiferromagetic state. The magnetoresistance behavior is consistent with the above conclusions.

  6. Magnetic behavior of Gd3Ru4Al12, a layered compound with distorted kagomé net.

    PubMed

    Chandragiri, Venkatesh; Iyer, Kartik K; Sampathkumaran, E V

    2016-05-27

    The magnetic behavior of the compound, Gd3Ru4Al12, which was reported about two decades ago to crystallize in a hexagonal structure (space group P63/mmc), has not been investigated in the past literature despite interesting structural features (that is, magnetic layers and triangular as well as kagomé-lattice features favoring frustrated magnetism) characterizing this compound. We report here the results of studies of magnetization, heat capacity and magnetoresistance in the temperature range T  =  1.8-300 K. The results establish that there is a long-range magnetic order of antiferromagnetic type below (T N  =) 18.5 K, despite a much larger value (~80 K) of paramagnetic Curie temperature with a positive sign characteristic of ferromagnetic interaction. We attribute this to geometric frustration. The most interesting finding is that there is an additional magnetic anomaly below ~55 K before the onset of long-range order in the magnetic susceptibility data. Concurrent with this observation, the sign of isothermal change in entropy, ΔS  =  S(0)  -  S(H), where H is the externally applied magnetic field, remains positive above T N, with a broad peak. This observation indicates the presence of ferromagnetic clusters before the onset of long-range magnetic order. Thus, this compound may serve as an example of a situation in which magnetic frustration due to geometrical reasons faces competition from such magnetic precursor effects. There is also a reversal of the sign of  -ΔS in the curves for lower final fields (H  <  30 kOe) on entering the magnetically ordered state consistent with the entrance to an antiferromagetic state. The magnetoresistance behavior is consistent with the above conclusions.

  7. Functional roles of gangliosides in neurodevelopment--An overview of recent advances

    PubMed Central

    Yu, Robert K.; Tsai, Yi-Tzang; Ariga, Toshio

    2013-01-01

    Summary Gangliosides are sialic acid-containing glycosphingolipids (GSLs) that are most abundant in the nervous system. They are localized primarily in the outer leaflets of plasma membranes and participated in cell-cell recognition, adhesion, and signal transduction and are integral components of cell surface microdomains or lipid rafts along with proteins, sphingomyelin and cholesterol. Ganglioside-rich lipid rafts play an important role in signaling events affecting neural development and the pathogenesis of certain diseases. Disruption of ganglioside synthase genes in mice induces developmental defects and neural degeneration. Targeting ganglioside metabolism may represent a novel therapeutic strategy for intervention in certain diseases. In this review, we focus on recent advances on metabolic and functional studies of gangliosides in normal brain development and in certain neurological disorders. PMID:22410735

  8. Studies of the spin-Hamiltonian parameters and defect structures for Gd3+ ions in zircon-structure silicates MSiO4 (M=Zr, Hf, Th).

    PubMed

    Yang, Wei-Qing; Zheng, Wen-Chen

    2011-09-01

    The spin-Hamiltonian parameters (g factors g∥, g⊥ and zero-field splittings b2(0), b4(0), b4(4), b6(0), b6(4)) for 4f7 ion Gd3+ at the tetragonal M4+ site of zircon-structure silicates MSiO4 (M=Zr, Hf, Th) are calculated from a diagonalization (of energy matrix) method. The Hamiltonian concerning this energy matrix contains the free-ion, crystal-field interaction and Zeeman interaction terms and the 56×56 energy matrix is constructed by considering the ground multiplet 8S7/2 and the excited multiplets 6L7/2 (L=P, D, F, G, H, I). The defect structures of Gd3+ centers in the three MSiO4 crystals are yielded from the calculation. The results are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Effects of doping concentration and co-doping with cerium on the luminescence properties of Gd3Ga5O12:Cr3+ for thermometry applications

    NASA Astrophysics Data System (ADS)

    Pareja, Jhon; Litterscheid, Christian; Molina, Alejandro; Albert, Barbara; Kaiser, Bernhard; Dreizler, Andreas

    2015-09-01

    The accuracy of surface temperature measurements using thermographic phosphors relies on an extensive knowledge of the temperature-dependent properties of the phosphor. This paper addresses the effects of doping concentration and co-doping with cerium on the luminescence properties of the Gd3Ga5O12:Cr3+ phosphor. High-crystallinity Gd3Ga5O12:Cr3+,Ce3+ powder samples (GGG:Cr,Ce) with different Cr3+ and Ce3+ concentrations were synthesized, and their luminescence spectra as well as their decay lifetime properties were characterized after UV laser excitation. Results revealed that the concentration quenching decreases the luminescence lifetime at concentrations above 0.5 mol% Cr3+ while the emission spectrum remains independent of the Cr3+ concentration. Co-doping with small amounts of Ce3+ improves the temperature-dependent luminescence characteristics by reducing the afterglow and producing fairly mono-exponential luminescence decays without changing the lifetime.

  10. Origin of improved scintillation efficiency in (Lu,Gd)3(Ga,Al)5O12:Ce multicomponent garnets: An X-ray absorption near edge spectroscopy study

    NASA Astrophysics Data System (ADS)

    Wu, Yuntao; Luo, Jialiang; Nikl, Martin; Ren, Guohao

    2014-01-01

    In the recent successful improvement of scintillation efficiency in Lu3Al5O12:Ce driven by Ga3+ and Gd3+ admixture, the "band-gap engineering" and energy level positioning have been considered the valid strategies so far. This study revealed that this improvement was also associated with the cerium valence instability along with the changes of chemical composition. By utilizing X-ray absorption near edge spectroscopy technique, tuning the Ce3+/Ce4+ ratio by Ga3+ admixture was evidenced, while it was kept nearly stable with the Gd3+ admixture. Ce valence instability and Ce3+/Ce4+ ratio in multicomponent garnets can be driven by the energy separation between 4f ground state of Ce3+ and Fermi level.

  11. Prevalence, specificity and functionality of anti-ganglioside antibodies in neuropathy associated with IgM monoclonal gammopathy.

    PubMed

    Stork, Abraham C J; Jacobs, Bart C; Tio-Gillen, Anne P; Eurelings, Marijke; Jansen, Marc D; van den Berg, Leonard H; Notermans, Nicolette C; van der Pol, W-Ludo

    2014-03-15

    IgM antibodies against gangliosides and their complexes were studied in sera from 54 patients with polyneuropathy and IgM monoclonal gammopathy (IgM-PNP) without anti-MAG antibodies. Anti-ganglioside antibodies were found in 19 (35%) patients. Five (9%) patients had antibodies against ganglioside complexes. IgM antibodies against gangliosides activated complement in vitro. Light chain usage was restricted to kappa or lambda in most, but not all patients. In conclusion, anti-ganglioside antibodies in IgM-PNP are common, display pathogenic properties and do not always arise from a monoclonal B cell proliferation.

  12. Conjugation of glucosamine with Gd3+-based nanoporous silica using a heterobifunctional ANB-NOS crosslinker for imaging of cancer cells

    PubMed Central

    Mehravi, Bita; Ahmadi, Mohsen; Amanlou, Massoud; Mostaar, Ahmad; Ardestani, Mehdi Shafiee; Ghalandarlaki, Negar

    2013-01-01

    Background The aim of this study was to synthesize Gd3+-based silica nanoparticles that conjugate easily with glucosamine and to investigate their use as a nanoprobe for detection of human fibrosarcoma cells. Methods Based on the structure of the 2-fluoro-2-deoxy-D-glucose molecule (18FDG), a new compound consisting of D-glucose (1.1 nm) was conjugated with a Gd3+-based mesoporous silica nanoparticle using an N-5-azido-2-nitrobenzoyloxy succinimide (ANB-NOS) crosslinker The contrast agent obtained was characterized using a variety of methods, including Fourier transform infrared spectroscopy, nitrogen physisorption, thermogravimetric analysis, scanning and transmission electron microscopy, and inductively coupled plasma atomic emission spectrometry (ICP-AES). In vitro studies included cell toxicity, apoptosis, tumor necrosis factor-alpha, and hexokinase assays, and in vivo tests consisted of evaluation of blood glucose levels using the contrast compound and tumor imaging. The cellular uptake study was validated using ICP-AES. Magnetic resonance relaxivity of the contrast agent was determined using a 1.5 Tesla scanner. Results ANB-NOS was found to be the preferred linker for attaching glucosamine onto the surface of the mesoporous silica nanospheres. The r1 relaxivity for the nanoparticles was 17.70 mM−1s−1 per Gd3+ ion, which is 4.4 times larger than that for Magnevist® (r1 approximately 4 mM−1s−1 per Gd3+ ion). The compound showed suitable cellular uptake (75.6% ± 2.01%) without any appreciable cytotoxicity. Conclusion Our results suggest that covalently attaching glucosamine molecules to mesoporous silica nanoparticles enables effective targeted delivery of a contrast agent. PMID:24101868

  13. Growth and scintillation properties of 3 in. diameter Ce doped Gd3Ga3Al2O12 scintillation single crystal

    NASA Astrophysics Data System (ADS)

    Kamada, Kei; Shoji, Yasuhiro; Kochurikhin, Vladimir V.; Okumura, Satoshi; Yamamoto, Seiichi; Nagura, Aya; Yeom, Jung Yeol; Kurosawa, Shunsuke; Yokota, Yuui; Ohashi, Yuji; Nikl, Martin; Yoshikawa, Akira

    2016-10-01

    The 3 in. size Ce1%:Gd3Al2Ga3O12 single crystals were prepared by the Czochralski (Cz) method. Optical constants were measured. Chemical composition analysis and uniformity of scintillation decay and light yield along growth direction were evaluated. The timing resolution measurement for a pair of 3 mm×3 mm×3 mm size Ce:GAGG scintillator crystals was performed using Si-PMs.

  14. Silicon-Induced UV Transparency in Phosphate Glasses and Its Application to the Enhancement of the UV Type B Emission of Gd(3).

    PubMed

    Jiménez, José A

    2017-05-10

    The silicon route to improve the ultraviolet (UV) transparency in phosphate glasses is investigated and further exploited to enhance the UV type B (280-320 nm) emission of gadolinium(III) relevant for biomedical applications. The glasses were synthesized with a barium phosphate composition by melt-quenching in ambient atmosphere and the optical properties investigated by optical absorption and photoluminescence (PL) spectroscopy including emission decay kinetics. An improvement in the UV transparency was gradually developed for the glasses melted merely with increasing amounts of Si powder. A particular PL in the visible was also exhibited for such glasses under excitation at 275 nm, consistent with the presence of Si-induced defects. For Si-Gd codoped glasses, the UV transparency was likewise manifested, while the UV emission from Gd(3+) around 312 nm was enhanced with the increase in Si concentration (up to ∼6.7 times). Moreover, along with the Gd(3+) PL intensity enhancement, a linear correlation was revealed between the increase in decay times for the Gd(3+6)P7/2-emitting state and the amount of silicon. It is then suggested that the improved PL properties of gadolinium(III) originate from the increased UV transparency of the host and the consequent precluding of a nonradiative energy transfer from Gd(3+) to the matrix. Accordingly, a role of Si as PL quenching inhibitor is supported. The demonstrated efficacy of the Si-Gd codoping concept realized by a facile glass synthesis procedure may appeal to the application of the UV-emitting glasses for phototherapy lamps.

  15. Imaging Mass Spectrometry Technology and Application on Ganglioside Study; Visualization of Age-Dependent Accumulation of C20-Ganglioside Molecular Species in the Mouse Hippocampus

    PubMed Central

    Sugiura, Yuki; Shimma, Shuichi; Konishi, Yoshiyuki; Yamada, Maki K.; Setou, Mitsutoshi

    2008-01-01

    Gangliosides are particularly abundant in the central nervous system (CNS) and thought to play important roles in memory formation, neuritogenesis, synaptic transmission, and other neural functions. Although several molecular species of gangliosides have been characterized and their individual functions elucidated, their differential distribution in the CNS are not well understood. In particular, whether the different molecular species show different distribution patterns in the brain remains unclear. We report the distinct and characteristic distributions of ganglioside molecular species, as revealed by imaging mass spectrometry (IMS). This technique can discriminate the molecular species, raised from both oligosaccharide and ceramide structure by determining the difference of the mass-to-charge ratio, and structural analysis by tandem mass spectrometry. Gangliosides in the CNS are characterized by the structure of the long-chain base (LCB) in the ceramide moiety. The LCB of the main ganglioside species has either 18 or 20 carbons (i.e., C18- or C20-sphingosine); we found that these 2 types of gangliosides are differentially distributed in the mouse brain. While the C18-species was widely distributed throughout the frontal brain, the C20-species selectively localized along the entorhinal-hippocampus projections, especially in the molecular layer (ML) of the dentate gyrus (DG). We revealed development- and aging-related accumulation of the C-20 species in the ML-DG. Thus it is possible to consider that this brain-region specific regulation of LCB chain length is particularly important for the distinct function in cells of CNS. PMID:18800170

  16. The Gadolinium (Gd(3+)) and Tin (Sn(4+)) Co-doped BiFeO3 Nanoparticles as New Solar Light Active Photocatalyst.

    PubMed

    Irfan, Syed; Rizwan, Syed; Shen, Yang; Li, Liangliang; Asfandiyar; Butt, Sajid; Nan, Ce-Wen

    2017-02-14

    The process of photocatalysis is appealing to huge interest motivated by the great promise of addressing current energy and environmental issues through converting solar light directly into chemical energy. However, an efficient solar energy harvesting for photocatalysis remains a critical challenge. Here, we reported a new full solar spectrum driven photocatalyst by co-doping of Gd(3+) and Sn(4+) into A and B-sites of BiFeO3 simultaneously. The co-doping of Gd(3+) and Sn(4+) played a key role in hampering the recombination of electron-hole pairs and shifted the band-gap of BiFeO3 from 2.10 eV to 2.03 eV. The Brunauer-Emmett-Teller (BET) measurement confirmed that the co-doping of Gd(3+) and Sn(4+) into BiFeO3 increased the surface area and porosity, and thus the photocatalytic activity of the Bi0.90Gd0.10Fe0.95Sn0.05O3 system was significantly improved. Our work proposed a new photocatalyst that could degrade various organic dyes like Congo red, Methylene blue, and Methyl violet under irradiation with different light wavelengths and gave guidance for designing more efficient photocatalysts.

  17. W-band orientation selective DEER measurements on a Gd3+/nitroxide mixed-labeled protein dimer with a dual mode cavity

    NASA Astrophysics Data System (ADS)

    Kaminker, Ilia; Tkach, Igor; Manukovsky, Nurit; Huber, Thomas; Yagi, Hiromasa; Otting, Gottfried; Bennati, Marina; Goldfarb, Daniella

    2013-02-01

    Double electron-electron resonance (DEER) at W-band (95 GHz) was applied to measure the distance between a pair of nitroxide and Gd3+ chelate spin labels, about 6 nm apart, in a homodimer of the protein ERp29. While high-field DEER measurements on systems with such mixed labels can be highly attractive in terms of sensitivity and the potential to access long distances, a major difficulty arises from the large frequency spacing (about 700 MHz) between the narrow, intense signal of the Gd3+ central transition and the nitroxide signal. This is particularly problematic when using standard single-mode cavities. Here we show that a novel dual-mode cavity that matches this large frequency separation dramatically increases the sensitivity of DEER measurements, allowing evolution times as long as 12 μs in a protein. This opens the possibility of accessing distances of 8 nm and longer. In addition, orientation selection can be resolved and analyzed, thus providing additional structural information. In the case of W-band DEER on a Gd3+-nitroxide pair, only two angles and their distributions have to be determined, which is a much simpler problem to solve than the five angles and their distributions associated with two nitroxide spin labels.

  18. Facile preparation of Gd3+ doped carbon quantum dots: Photoluminescence materials with magnetic resonance response as magnetic resonance/fluorescence bimodal probes

    NASA Astrophysics Data System (ADS)

    Ren, X. Y.; Yuan, X. X.; Wang, Y. P.; Liu, C. L.; Qin, Y.; Guo, L. P.; Liu, L. H.

    2016-07-01

    There are a few bimodal molecular imaging probes constructed by gadolinium (3+) ions in combination with carbon quantum dots (CQDs), and the reported ones show such obvious drawbacks as low luminous efficiency and weak MRI contrast. In the paper, a kind of CQDs photoluminescence materials with magnetic resonance response was prepared by hydrothermal method and employing gadopentetate monomeglumine (GdPM) as a precusor. Here, the GdPM plays a role of not only carbon source, but also gadolinium (3+) sources. When the GdPM aqueous solution with a concentration of 4 mg mL-1 was pyrolyzed under 220 °C and 2.0 MPa for 8 h, an optimal CQDs was obtained which are doped with gadolinium (3+) ions in both chelates and Gd2O3 (named as Gd3+-CQDs). The average diameter of the Gd3+-CQDs is about 1.6 nm, which show a high photoluminescence quantum yield of 7.1%, as well as high longitudinal relaxivity (r1) of 9.87 mM-1 s-1. And owing to the unconspicuous cell toxicity, the Gd3+-CQDs show big possibility for clinical application in magnetic resonance/fluorescence bimodal molecular imaging.

  19. W-band orientation selective DEER measurements on a Gd3+/nitroxide mixed-labeled protein dimer with a dual mode cavity.

    PubMed

    Kaminker, Ilia; Tkach, Igor; Manukovsky, Nurit; Huber, Thomas; Yagi, Hiromasa; Otting, Gottfried; Bennati, Marina; Goldfarb, Daniella

    2013-02-01

    Double electron-electron resonance (DEER) at W-band (95 GHz) was applied to measure the distance between a pair of nitroxide and Gd(3+) chelate spin labels, about 6 nm apart, in a homodimer of the protein ERp29. While high-field DEER measurements on systems with such mixed labels can be highly attractive in terms of sensitivity and the potential to access long distances, a major difficulty arises from the large frequency spacing (about 700 MHz) between the narrow, intense signal of the Gd(3+) central transition and the nitroxide signal. This is particularly problematic when using standard single-mode cavities. Here we show that a novel dual-mode cavity that matches this large frequency separation dramatically increases the sensitivity of DEER measurements, allowing evolution times as long as 12 μs in a protein. This opens the possibility of accessing distances of 8 nm and longer. In addition, orientation selection can be resolved and analyzed, thus providing additional structural information. In the case of W-band DEER on a Gd(3+)-nitroxide pair, only two angles and their distributions have to be determined, which is a much simpler problem to solve than the five angles and their distributions associated with two nitroxide spin labels. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. EPR detected polarization transfer between Gd3+ and protons at low temperature and 3.3 T: The first step of dynamic nuclear polarization

    NASA Astrophysics Data System (ADS)

    Nagarajan, Vijayasarathi; Hovav, Yonatan; Feintuch, Akiva; Vega, Shimon; Goldfarb, Daniella

    2010-06-01

    Electron-electron double resonance pulsed electron paramagnetic resonance (EPR) at 95 GHz (3.3 T) is used to follow the dynamics of the electron spin polarization during the first stages of dynamic nuclear polarization in solids. The experiments were performed on a frozen solution of Gd+3 (S =7/2) in water/glycerol. Focusing on the central |-1/2⟩→|+1/2⟩ transition we measured the polarization transfer from the Gd3+ electron spin to the adjacent H1 protons. The dependence of the echo detected EPR signal on the length of the microwave irradiation at the EPR "forbidden" transition corresponding to an electron and a proton spin flip is measured for different powers, showing dynamics on the microsecond to millisecond time scales. A theoretical model based on the spin density matrix formalism is suggested to account for this dynamics. The central transition of the Gd3+ ion is considered as an effective S =1/2 system and is coupled to H1 (I =1/2) nuclei. Simulations based on a single electron-single nucleus four level system are shown to deviate from the experimental results and an alternative approach taking into account the more realistic multinuclei picture is shown to agree qualitatively with the experiments.

  1. Pulse shape discrimination properties of Gd3Ga3Al2O12:Ce,B single crystal in comparison with CsI:Tl

    NASA Astrophysics Data System (ADS)

    Rawat, S.; Tyagi, Mohit; Netrakanti, P. K.; Kashyap, V. K. S.; Mitra, A.; Singh, A. K.; Desai, D. G.; Kumar, G. Anil; Gadkari, S. C.

    2016-12-01

    Single crystals of Gd3Ga3Al2O12:Ce,B and CsI:Tl were grown by Czochralski and Bridgman techniques, respectively. While both the crystals exhibited similar emission at about 550 nm, their scintillation decay times showed significantly different characteristics. The average scintillation decay time of Gd3Ga3Al2O12:Ce,B crystal was found to be about 284 ns for alpha excitation compared to 108 ns measured for a gamma source. On the other hand in CsI:Tl crystals, the alpha excitation resulted in a lower average decay time of 600 ns compared to 1200 ns with gamma excitation. Their pulse shape discrimination (PSD) for gamma and alpha radiations were studied by coupling the scintillators with photomultiplier tube or SiPM and employing an advanced digitizer as well as a conventional zero-crossing setup. In spite of having a poor α/γ light yield ratio, the PSD figure of merit and the difference of zero-crossing time in Gd3Ga3Al2O12:Ce,B crystals were found to be superior in comparison to CsI:Tl crystals.

  2. The Gadolinium (Gd3+) and Tin (Sn4+) Co-doped BiFeO3 Nanoparticles as New Solar Light Active Photocatalyst

    PubMed Central

    Irfan, Syed; Rizwan, Syed; Shen, Yang; Li, Liangliang; Asfandiyar, A; Butt, Sajid; Nan, Ce-Wen

    2017-01-01

    The process of photocatalysis is appealing to huge interest motivated by the great promise of addressing current energy and environmental issues through converting solar light directly into chemical energy. However, an efficient solar energy harvesting for photocatalysis remains a critical challenge. Here, we reported a new full solar spectrum driven photocatalyst by co-doping of Gd3+ and Sn4+ into A and B-sites of BiFeO3 simultaneously. The co-doping of Gd3+ and Sn4+ played a key role in hampering the recombination of electron-hole pairs and shifted the band-gap of BiFeO3 from 2.10 eV to 2.03 eV. The Brunauer-Emmett-Teller (BET) measurement confirmed that the co-doping of Gd3+ and Sn4+ into BiFeO3 increased the surface area and porosity, and thus the photocatalytic activity of the Bi0.90Gd0.10Fe0.95Sn0.05O3 system was significantly improved. Our work proposed a new photocatalyst that could degrade various organic dyes like Congo red, Methylene blue, and Methyl violet under irradiation with different light wavelengths and gave guidance for designing more efficient photocatalysts. PMID:28195198

  3. Substitution of Y3+ for Gd3+ on the luminescent properties of BaGd2O4:Eu3+ scintillating phosphors

    NASA Astrophysics Data System (ADS)

    Sun, Xin-Yuan; Liu, Yu; Liu, Xiao-Lin; Cao, Ren-Ping; Li, Yu-Nong; Lin, Liang-Wu

    2014-07-01

    The BaGd1.8-xYxEu0.2O4 (0 ⩽ x ⩽ 1.8) phosphors were synthesized by the conventional high temperature solid-state reaction (SSR) method at 1300 °C in air. The structure and optical performances of the as-synthesized phosphors were characterized using X-ray powder diffraction (XRD), excitation and emission spectra, X-ray excited luminescence (XEL) and thermoluminescence (TL) spectra. The XRD results reveal that the structure of the BaGd2O4 host are not alternated by the gradual substitution of Y3+ for Gd3+ ions. Both energy transfer and competitive absorption between Gd3+ and Eu3+ ions may coexist by the excitation and emission spectra. The XEL intensity increases with the elevated substitution ratios, i.e. the x values. The strongest XEL intensity increases by a factor of about 10 when compared with the x = 1.8 and x = 0.0 phosphors. The possible mechanism of enhancing Eu3+ emission was also discussed by the TL properties of BaGd1.8-xYxEu0.2O4 phosphors by the gradual substitution of Y3+ for Gd3+ ions.

  4. Synthesis, characterization and luminescence studies in ZrO2:Dy3+ and ZrO2:Dy3+, Gd3+ films deposited by the Pyrosol method

    NASA Astrophysics Data System (ADS)

    Martínez-Olmos, R. C.; Guzmán-Mendoza, J.; Báez-Rodríguez, A.; Álvarez-Fragoso, O.; García-Hipólito, M.; Falcony, C.

    2015-08-01

    ZrO2, ZrO2:Dy3+ and ZrO2:Dy3+, Gd3+ films were synthesized using the Pyrosol technique. These films have a ZrO2-metastable tetragonal crystalline structure, which is better defined as the deposition temperature increases. Photoluminescence and cathodoluminescence properties of these films were studied as a function of deposition parameters such as substrate temperature and Dy3+ and Gd3+ relative concentrations. All luminescent emission spectra showed the typical electronic transitions 4f → 4f of the Dy3+ ions at 480, 574 and 655 nm. The luminescent intensity is observed to increase with the Dy3+ ion concentration up to 7 at.% in the spraying solution (1.8 at.% inside films), higher concentration result in an inhibition of the luminescence. Incorporation of Gd3+ ions in ZrO2:Dy3+ films produced a marked increase in the luminescent emission intensity (approximately 15 times). The elemental composition and surface morphology of these films are also reported.

  5. The Gadolinium (Gd3+) and Tin (Sn4+) Co-doped BiFeO3 Nanoparticles as New Solar Light Active Photocatalyst

    NASA Astrophysics Data System (ADS)

    Irfan, Syed; Rizwan, Syed; Shen, Yang; Li, Liangliang; Asfandiyar; Butt, Sajid; Nan, Ce-Wen

    2017-02-01

    The process of photocatalysis is appealing to huge interest motivated by the great promise of addressing current energy and environmental issues through converting solar light directly into chemical energy. However, an efficient solar energy harvesting for photocatalysis remains a critical challenge. Here, we reported a new full solar spectrum driven photocatalyst by co-doping of Gd3+ and Sn4+ into A and B-sites of BiFeO3 simultaneously. The co-doping of Gd3+ and Sn4+ played a key role in hampering the recombination of electron-hole pairs and shifted the band-gap of BiFeO3 from 2.10 eV to 2.03 eV. The Brunauer-Emmett-Teller (BET) measurement confirmed that the co-doping of Gd3+ and Sn4+ into BiFeO3 increased the surface area and porosity, and thus the photocatalytic activity of the Bi0.90Gd0.10Fe0.95Sn0.05O3 system was significantly improved. Our work proposed a new photocatalyst that could degrade various organic dyes like Congo red, Methylene blue, and Methyl violet under irradiation with different light wavelengths and gave guidance for designing more efficient photocatalysts.

  6. Effect of Mg2+ ions co-doping on timing performance and radiation tolerance of Cerium doped Gd3Al2Ga3O12 crystals

    NASA Astrophysics Data System (ADS)

    Lucchini, M. T.; Babin, V.; Bohacek, P.; Gundacker, S.; Kamada, K.; Nikl, M.; Petrosyan, A.; Yoshikawa, A.; Auffray, E.

    2016-04-01

    Inorganic scintillators with high density and high light yield are of major interest for applications in medical imaging and high energy physics detectors. In this work, the optical and scintillation properties of Mg co-doped Ce:Gd3Al2Ga3O12 crystals, grown using Czochralski technique, have been investigated and compared with Ce:Gd3Al2Ga3O12 ones prepared with identical technology. Improvements in the timing performance of the Mg co-doped samples with respect to Ce:Gd3Al2Ga3O12 ones have been measured, namely a substantial shortening of the rise time and scintillation decay components and lower afterglow were achieved. In particular, a significantly better coincidence time resolution of 233 ps FWHM, being a fundamental parameter for TOF-PET devices, has been observed in Mg co-doped crystals. The samples have also shown a good radiation tolerance under high doses of γ-rays, making them suitable candidates for applications in harsh radiation environments, such as detectors at future collider experiments.

  7. Enhanced UVB emission and analysis of chemical states of Ca5(PO4)3OH:Gd3+,Pr3+ phosphor prepared by co-precipitation

    NASA Astrophysics Data System (ADS)

    Mokoena, P. P.; Nagpure, I. M.; Kumar, Vinay; Kroon, R. E.; Olivier, E. J.; Neethling, J. H.; Swart, H. C.; Ntwaeaborwa, O. M.

    2014-08-01

    Hydroxyapatite (Ca5(PO4)3OH) is a well-known bioceramic material used in medical applications because of its ability to form direct chemical bonds with living tissues. This mineral is currently used as a host for rare-earth ions (e.g. Gd3+, Pr3+, Tb3+, etc.) to prepare phosphors that can be used in light emitting devices of different types. In this study Ca5(PO4)3OH:Gd3+,Pr3+ phosphors were prepared by the co-precipitation method and were characterised by x-ray diffraction, x-ray photoelectron spectroscopy, scanning electron microscopy, high resolution transmission electron microscopy, energy dispersive x-ray spectroscopy and photoluminescence spectroscopy. The x-ray diffraction pattern was consistent with the hexagonal phase of Ca5(PO4)3OH referenced in JCPDS card number 73-0293. The x-ray photoelectron spectroscopy data indicated that Ca2+ occupied two different lattice sites, referred to as Ca1 and Ca2. The photoluminescence data exhibited a narrowband emission located at 313 nm, which is associated with the 6P7/2→8S7/2 transition of the Gd3+ ion. This emission is classified as ultraviolet B and it is suitable for use in phototherapy lamps to treat various skin diseases. The photoluminescence intensity of the 313 nm emission was enhanced considerably by Pr3+ co-doping.

  8. Expression of the human CMP-NeuAc:GM3 alpha2,8-sialyltransferase (GD3 synthase) gene through the NF-kappaB activation in human melanoma SK-MEL-2 cells.

    PubMed

    Kang, Nam-Young; Kim, Cheorl-Ho; Kim, Kyoung-Sook; Ko, Jeong-Heon; Lee, Jai-Heon; Jeong, Yong-Kee; Lee, Young-Choon

    2007-01-01

    To elucidate the mechanism underlying the regulation of human GD3 synthase gene expression in human melanoma SK-MEL-2 cells, we identified the promoter region of the human GD3 synthase gene. The 5'-rapid amplification of cDNA end (5'-RACE) using mRNA prepared from SK-MEL-2 cells revealed the presence of multiple transcription start sites of human GD3 synthase gene. Promoter analyses of the 5'-flanking region of the human GD3 synthase gene using luciferase gene reporter system showed the strong promoter activity in SK-MEL-2 cells. Deletion study revealed that the region as the core promoter from -1146 to -646 (A of the translational start ATG as position +1) was indispensable for endogenous expression of human GD3 synthase gene. This region lacks apparent TATA and CAAT boxes but contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1 and NF-kappaB. Electrophoretic mobility shift assays using specific competitors, chromatin immunoprecipitation assay and site-directed mutagenesis demonstrated that only NF-kappaB element in this region is required for the promoter activity in SK-MEL-2 cells. These results indicate that NF-kappaB plays an essential role in the transcriptional activity of human GD3 synthase gene essential for GD3 synthesis in SK-MEL-2 cells.

  9. Proton NMR study of spin dynamics in the magnetic organic chains M (hfac)3 NITEt (M =Eu3 +,Gd3 + )

    NASA Astrophysics Data System (ADS)

    Mariani, M.; Lascialfari, A.; Caneschi, A.; Ammannato, L.; Gatteschi, D.; Rettori, A.; Pini, M. G.; Cucci, C.; Borsa, F.

    2016-04-01

    In this work, we present a nuclear magnetic resonance (NMR) study of the spin dynamics in the rare-earth-based low-dimensional molecular magnetic chains Eu (hfac) 3NITEt and Gd (hfac) 3NITEt (in short, Eu-Et and Gd-Et). Although both samples are based on the same chemical building block, [(hfac) 3NITEt ] , their magnetic properties change dramatically when the Eu3 + ion, which is nonmagnetic at low temperatures, is substituted by the magnetic Gd3 + ion. The present proton NMR investigation shows that, down to the lowest investigated temperature (T =1.5 K for Gd-Et and T =3 K for Eu-Et), the Eu-Et chain behaves as a one-dimensional Heisenberg model with antiferromagnetic exchange coupling (J =-20 K) between s =1 /2 organic radicals, and has a T -independent exchange frequency (ωe=2.6 ×1012 rad/s). In the Gd-Et chain, in contrast, a competition arises between nearest-neighbor ferromagnetic coupling and next-nearest-neighbor antiferromagnetic coupling; moreover, two phase transitions have previously been found, in agreement with Villain's conjecture: a first transition, at T0=2.2 K, from a high temperature paramagnetic phase to a chiral spin liquid phase, and a second transition, at TN=1.9 K, to a three-dimensional helical spin solid phase. Contrary to the Eu-Et chain (whose three-dimensional ordering temperature is estimated to insurge at very low, TN≈0.3 K), critical spin dynamics effects have been measured in the Gd-Et chain on approaching TN=1.9 K: namely, a divergence of the proton nuclear spin-lattice relaxation rate 1 /T1 , which in turn produces a sudden wipe-out of the NMR signal in a very narrow (Δ T ˜0.04 K) temperature range above TN. Below TN, an inhomogeneous broadening of the NMR line indicates a complete spin freezing. At T0=2.2 K, instead, such critical effects are not observed because NMR measurements probe the two-spin correlation function, while the chiral spin liquid phase transition is associated with a divergence of the four

  10. Synthesis, Crystal Structure, Magnetism, and Optical Properties of Gd 3[SiON 3]O—An Oxonitridosilicate Oxide with Noncondensed SiON 3 Tetrahedra

    NASA Astrophysics Data System (ADS)

    Höppe, Henning A.; Kotzyba, Gunter; Pöttgen, Rainer; Schnick, Wolfgang

    2002-09-01

    The novel oxonitridosilicate oxide (sion oxide) Gd 3[SiON 3]O was obtained by the reaction of gadolinium metal with its carbonate oxide and silicon diimide in a radiofrequency (r.f.) furnace at a temperature of 1400°C. The crystal structure of Gd 3[SiON 3]O ( I4/ mcm, a=649.1(2) pm, c=1078.8(6) pm, Z=4, R1=0.0411, w R2=0.0769, 405 F2 values, 19 parameters, 123 K) is isotypic with that of Ba 3[SiO 4]O and Cs 3[CoCl 4]Cl. It can be derived from the perovskite structure type by a hierarchical substitution: Ti 4+→O 2-, O 2-→Gd 3+, Ca 2+→[SiON 3] 7- resulting in the formation of large [OGd 6] 16+ octahedra, which are twisted by ξ=16.47(1)° around [001]. The low-temperature single-crystal data investigation led to a crystallographic splitting of the central O atom which could not be resolved at room temperature. The UV-Vis absorption spectra in reflection geometry of the yellow title compound revealed two overlaying broad bands, one peaking at almost the same wavelength as observed in gadolinium oxide (340 nm) and a second red-shifted band at approximately 400 nm indicating a strong influence of nitrogen on the ligand field splitting of the 5 d states of Gd 3+. Temperature-dependent magnetic susceptibility measurements of Gd 3[SiON 3]O show Curie-Weiss behavior from 2 to 300 K with an experimental magnetic moment of 7.68(5) μB/Gd, indicating trivalent gadolinium. There is no evidence for magnetic ordering down to 2 K. According to the paramagnetic Curie temperature of -7(1) K, the exchange between the gadolinium magnetic moments is supposed to be only weak. The vibrational spectroscopic data (IR and Raman) are reported.

  11. Direct evidence that ganglioside is an integral component of the thyrotropin receptor

    SciTech Connect

    Kielczynski, W.; Harrison, L.C.; Leedman, P.J. )

    1991-03-01

    Gangliosides were extracted from purified human and porcine thyrotropin (TSH) receptors (TSH-R) and were detected by probing with an {sup 125}I-labeled sialic acid-specific lectin, Limax flavus agglutinin. Gangliosides copurified with human and porcine TSH-R migrated between monosialoganglioside GM1 and disialoganglioside GD1a. Ceramide glycanase digestion of the purified human TSH-R-associated glycolipid confirmed its ganglioside nature. It was resistant to Vibrio cholerae sialidase, which digest all gangliosides except GM1, but was sensitive to Arthrobacter ureafaciens sialidase, which digests all gangliosides including GM1. These findings indicate that the human TSH-R contains ganglioside that belongs to the galactosyl({beta}1{r arrow} 3)-N-acetylgalactosaminyl({beta}1{r arrow} 4)-(N-acetylneuraminyl({alpha}2{r arrow} 3))galactosyl({beta}1 {r arrow} 4)glucosyl({beta}1 {r arrow} 1)ceramide (GM1) family. Its intimate association with receptor protein implies a key role for ganglioside in the structure and function of the TSH-R.

  12. Changes in Liver Ganglioside Metabolism in Obstructive Cholestasis - the Role of Oxidative Stress.

    PubMed

    Šmíd, V; Petr, T; Váňová, K; Jašprová, J; Šuk, J; Vítek, L; Šmíd, F; Muchová, L

    2016-01-01

    Bile acids have been implicated in cholestatic liver damage, primarily due to their detergent effect on membranes and induction of oxidative stress. Gangliosides can counteract these harmful effects by increasing the rigidity of the cytoplasmic membrane. Induction of haem oxygenase (HMOX) has been shown to protect the liver from increased oxidative stress. The aim of this study was to determine the changes in the synthesis and distribution of liver gangliosides following bile duct ligation (BDL), and to assess the effects of HMOX both on cholestatic liver injury and ganglioside metabolism. Compared to controls, BDL resulted in a significant increase in total as well as complex gangliosides and mRNA expression of corresponding glycosyltransferases ST3GalV, ST8SiaI and B3GalTIV. A marked shift of GM1 ganglioside from the intracellular compartment to the cytoplasmic membrane was observed following BDL. Induction of oxidative stress by HMOX inhibition resulted in a further increase of these changes, while HMOX induction prevented this effect. Compared to BDL alone, HMOX inhibition in combination with BDL significantly increased the amount of bile infarcts, while HMOX activation decreased ductular proliferation. We have demonstrated that cholestasis is accompanied by significant changes in the distribution and synthesis of liver gangliosides. HMOX induction results in attenuation of the cholestatic pattern of liver gangliosides, while HMOX inhibition leads to the opposite effect.

  13. Exogenous gangliosides increase the release of brain-derived neurotrophic factor.

    PubMed

    Lim, Seung T; Esfahani, Kamilla; Avdoshina, Valeriya; Mocchetti, Italo

    2011-06-01

    Gangliosides are lipophilic compounds found in cell plasma membranes throughout the brain that play a role in neuronal plasticity and regeneration. Indeed, absence or abnormal accumulation of gangliosides has been shown to lead to neurological disorders. Experimental data have shown that exogenous gangliosides exhibit properties similar to the neurotrophins, a family of neurotrophic factors that are important in the survival and maintenance of neurons and prevention of neurological diseases. Brain-derived neurotrophic factor (BDNF) is the most abundant of the neurotrophins. This work was done to reveal the neurotrophic mechanism of exogenous gangliosides. In particular, we examined whether gangliosides promote the release of BDNF. Rat hippocampal neurons or human neuroblastoma cells were transduced with a recombinant adenovirus expressing BDNF-flag to facilitate detection of BDNF. Release of BDNF was then determined by Western blot analysis and a two-site immunoassay of culture medium. The depolarizing agent KCl was used as a comparison. In hippocampal neurons, both GM1 ganglioside and KCl evoked within minutes the release of mature BDNF. In human cells, GM1 and other gangliosides released both mature BDNF and pro-BDNF. The effect of gangliosides was structure-dependent. In fact, GT1b preferentially released mature BDNF whereas GM1 released both mature and pro-BDNF. Ceramide and sphingosine did not modify the release of BDNF. This work provides additional experimental evidence that exogenous gangliosides can be used to enhance the neurotrophic factor environment and promote neuronal survival in neurological diseases. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Targeting O-Acetyl-GD2 Ganglioside for Cancer Immunotherapy

    PubMed Central

    Fleurence, Julien; Fougeray, Sophie; Bahri, Meriem; Cochonneau, Denis; Clémenceau, Béatrice; Paris, François; Heczey, Andras

    2017-01-01

    Target selection is a key feature in cancer immunotherapy, a promising field in cancer research. In this respect, gangliosides, a broad family of structurally related glycolipids, were suggested as potential targets for cancer immunotherapy based on their higher abundance in tumors when compared with the matched normal tissues. GD2 is the first ganglioside proven to be an effective target antigen for cancer immunotherapy with the regulatory approval of dinutuximab, a chimeric anti-GD2 therapeutic antibody. Although the therapeutic efficacy of anti-GD2 monoclonal antibodies is well documented, neuropathic pain may limit its application. O-Acetyl-GD2, the O-acetylated-derivative of GD2, has recently received attention as novel antigen to target GD2-positive cancers. The present paper examines the role of O-acetyl-GD2 in tumor biology as well as the available preclinical data of anti-O-acetyl-GD2 monoclonal antibodies. A discussion on the relevance of O-acetyl-GD2 in chimeric antigen receptor T cell therapy development is also included. PMID:28154831

  15. Targeting O-Acetyl-GD2 Ganglioside for Cancer Immunotherapy.

    PubMed

    Fleurence, Julien; Fougeray, Sophie; Bahri, Meriem; Cochonneau, Denis; Clémenceau, Béatrice; Paris, François; Heczey, Andras; Birklé, Stéphane

    2017-01-01

    Target selection is a key feature in cancer immunotherapy, a promising field in cancer research. In this respect, gangliosides, a broad family of structurally related glycolipids, were suggested as potential targets for cancer immunotherapy based on their higher abundance in tumors when compared with the matched normal tissues. GD2 is the first ganglioside proven to be an effective target antigen for cancer immunotherapy with the regulatory approval of dinutuximab, a chimeric anti-GD2 therapeutic antibody. Although the therapeutic efficacy of anti-GD2 monoclonal antibodies is well documented, neuropathic pain may limit its application. O-Acetyl-GD2, the O-acetylated-derivative of GD2, has recently received attention as novel antigen to target GD2-positive cancers. The present paper examines the role of O-acetyl-GD2 in tumor biology as well as the available preclinical data of anti-O-acetyl-GD2 monoclonal antibodies. A discussion on the relevance of O-acetyl-GD2 in chimeric antigen receptor T cell therapy development is also included.

  16. Cutaneous dyspigmentation in patients with ganglioside GM3 synthase deficiency.

    PubMed

    Wang, Heng; Bright, Alicia; Xin, Baozhong; Bockoven, J R; Paller, Amy S

    2013-04-01

    Ganglioside GM3 synthase deficiency is a rare autosomal recessive metabolic disorder characterized by infantile onset of severe irritability and epilepsy, failure to thrive, developmental stagnation, and cortical blindness. Because of the lack of easily recognizable dysmorphism and specific neurologic manifestations, identification of patients with this condition is extremely challenging. Here we report on previously undescribed pigmentary abnormalities in 20 of 38 patients with GM3 synthase deficiency. All 20 of the patients showed freckle-like hyperpigmented macules, ranging in size from 2 to 5 mm in diameter and usually found bilaterally on the extremities, especially the dorsal aspects of the hands and feet. Seven of these patients also had depigmented macules and patches, especially on the face and extremities. These cutaneous changes were asymptomatic, and were not associated with the severity or particular phenotype of the neurologic disease. They became visible only after the first years of life with an increased incidence with advancing age. These distinct pigmentary features are not identified in 54 normal siblings, and may provide a useful clue in identifying patients with ganglioside metabolic disorders. Copyright © 2013 Wiley Periodicals, Inc.

  17. Recovery from Experimental Parkinsonism in Primates with GM1 Ganglioside Treatment

    NASA Astrophysics Data System (ADS)

    Schneider, J. S.; Pope, Anne; Simpson, Kimberly; Taggart, James; Smith, M. G.; Distefano, L.

    1992-05-01

    A parkinsonian syndrome can be produced in nonhuman primates by administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Parkinsonian-like symptoms induced acutely by MPTP were ameliorated after treatment with GM1 ganglioside, a substance shown to have neurotrophic effects on the damaged dopamine system in rodents. Treatment with GM1 ganglioside also increased striatal dopamine and metabolite levels and enhanced the dopaminergic innervation of the striatum as demonstrated by tyrosine hydroxylase immunohistochemistry. These results suggest that GM1 ganglioside may hold promise as a therapeutic agent for the treatment of Parkinson's disease.

  18. Isolation and structure of hematoside-type ganglioside from the starfish Linckia laevigata.

    PubMed

    Inagaki, Masanori; Saito, Takeshi; Miyamoto, Tomofumi; Higuchi, Ryuichi

    2009-02-01

    A hematoside-type ganglioside, LLG-1 (1), has been obtained from the polar lipid fraction of the chloroform/methanol extract of the starfish Linckia laevigata. The structure of the ganglioside has been determined on the basis of chemical and spectroscopic evidence as 1-O-[N-glycolyl-alpha-D-neuraminosyl-(2-->3)-beta-D-galactopyranosyl-(1-->4)-beta-D-glucopyranosyl]-ceramide. The ceramide moiety was composed of heterogeneous 2-hydroxy fatty acid and phytosphingosine units. This is the first report on the isolation and structure elucidation of naked hematoside-type ganglioside from echinoderms.

  19. The biologic role of ganglioside in neuronal differentiation--effects of GM1 ganglioside on human neuroblastoma SH-SY5Y cells.

    PubMed Central

    Lee, M. C.; Lee, W. S.; Park, C. S.; Juhng, S. W.

    1994-01-01

    Human neuroblastoma SH-SY5Y cell is a cloned cell line which has many attractive features for the study of neuronal proliferation and neurite outgrowth, because it has receptors for insulin, IGF-I and PDGF. Gangliosides are sialic acid containing glycosphingolipids which form an integral part of the plasma membrane of many mammalian cells. They inhibit cell growth mediated by tyrosine kinase receptors and ligand-stimulated tyrosine kinase activity, and autophosphorylation of EGF(epidermal growth factor) and PDGF receptors. The experiment was designed to study the effects of GM1 ganglioside on growth of human neuroblastoma SH-SY5Y cells stimulated with trophic factor in vitro. The cells were plated in Eagle's minimum essential medium without serum. The number and morphologic change of SH-SY5Y cells were evaluated in the serum free medium added GM1 ganglioside with insulin or PDGF. SH-SY5Y cells were maintained for six days in serum-free medium, and then cultured for over two weeks in serum-free medium containing either insulin or PDGF. The effect of insulin on cell proliferation developed earlier and was more potent than that of PDGF. These proliferative effects were inhibited by GM1 ganglioside, and the cells showed prominent neurites outgrowth. These findings suggest that GM1 ganglioside inhibits the cell proliferation mediated by tyrosine kinase receptors and directly induces neuritogenesis as one of the neurotrophic factors. PMID:7986393

  20. Study the effect of Gd3+ incorporation into nanocrystalline (Ni-Ti) substituted Mn-Zn ferrites on its structure and functional properties

    NASA Astrophysics Data System (ADS)

    Rady, K. E.; Shams, M. S.

    2017-03-01

    Ferrite samples with general chemical formula Mn0.9Zn0.1Ni0.05Ti0.05GdtFe1.9-tO4; (0.0≤ t≤0.05; step 0.01) were prepared using solid state reaction technique and the effect of Gd3+ ions incorporation on its physical properties has been studied. From the obtained results, XRD analysis reveals that the samples have a cubic spinel single phase structure for 0.0≤ t≤0.02; while for t≥0.03 a small peak of secondary phase (Gd3Fe5O12) appears and becomes more noticeable with increasing Gd content. The lattice parameter (a) of the prepared samples was found to be initially increases and then decreases with increasing Gd content which may be attributed to the difference in the ionic radii of the cations involved and the solubility limit of Gd3+ ions. The crystallite size of the samples was estimated using Scherrer's equation and ranged from 96 nm to 107 nm. A vibrating sample magnetometer (VSM) was used at room temperature in order to study the effect of Gd content on the magnetic hysteresis parameters of the prepared ferrites such as saturation magnetization and coercivity. DC molar magnetic susceptibility (χM) for the prepared samples was measured using Faraday's method as a function of temperature and the Curie temperature was calculated from the magnetic susceptibility measurements. Also the DC resistivity of the samples was measured at room temperature. The obtained results show that, the substitution by Gd3+ ions improves the electrical properties of the samples by increasing it DC electrical resistivity by 118% and consequently decreases it eddy current loss while the saturation magnetization slightly decreased by 14% only. The sample of t=0.01 shows a high dc magnetic susceptibility, high saturation magnetization (43.1 emu/g), high electric resistivity 12×103 Ω.m and high Curie temperature (496 K), which is useful in some technological applications such as transformer and inductor cores.

  1. The development of new phosphors of Tb3+/Eu3+ co-doped Gd3Al5O12 with tunable emission

    NASA Astrophysics Data System (ADS)

    Teng, Xin; Wang, Wenzhi; Cao, Zhentao; Li, Jinkai; Duan, Guangbin; Liu, Zongming

    2017-07-01

    The gadolinium aluminum garnets Gd3Al5O12 (GdAG) activated with Tb3+/Eu3+ were successfully prepared via co-precipitation method at 1500 °C in this work. The crystal structure stabilization, elements analysis, microphotograph, PL/PLE spectra, decay behavior and quantum efficiency were discussed in detail. The metastable GdAG compounds been effectively stabilized by doping with smaller 10 at.% Tb3+, which then allows the development of new phosphors of (Gd0.9-xTb0.1Eux)3Al5O12 (GdAG:Tb3+/Eu3+, x = 0-0.03) for opto-functionality explorations. The PLE/PL spectra displays that the strongest PLE peak was located at ∼276 nm, which overlaps the 8S7/2 → 6IJ transition of Gd3+. Under 276 nm excitation, the phosphors exhibited both Tb3+ and Eu3+ emissions at 548 nm (green, 5D4 → 7F5 transition of Tb3+) and 592 nm (orange-red, 5D0 → 7F1 transition of Eu3+), respectively. The emission intensities of Tb3+ and Eu3+ remarkably varied with the Eu3+ incorporation. As a consequence, the emission color can be readily tuned from approximately green to orange-red. Fluorescence decay analysis found that the lifetime for the Tb3+ emission rapidly decreased conforming to the Tb3+ → Eu3+ energy transfer, and the energy transfer efficiency was calculated. Owing to the Gd3+ → Eu3+ and Gd3+ → Tb3+ energy transfer, the emission intensities of Tb3+ and Eu3+ in (Gd0.9-xTb0.1Eux)AG phosphor were higher than (Y0.87Tb0.1Eu0.03)AG and (Lu0.87Tb0.1Eu0.03)AG system. The (Gd0.9-xTb0.1Eux)AG garnet phosphors developed in this work may serve as a new type of phosphor which hopefully meets the requirements of various lighting and optical display applications.

  2. Effects of gangliosides on the activity of the plasma membrane Ca2+-ATPase.

    PubMed

    Jiang, Lei; Bechtel, Misty D; Bean, Jennifer L; Winefield, Robert; Williams, Todd D; Zaidi, Asma; Michaelis, Elias K; Michaelis, Mary L

    2014-05-01

    Control of intracellular calcium concentrations ([Ca(2+)]i) is essential for neuronal function, and the plasma membrane Ca(2+)-ATPase (PMCA) is crucial for the maintenance of low [Ca(2+)]i. We previously reported on loss of PMCA activity in brain synaptic membranes during aging. Gangliosides are known to modulate Ca(2+) homeostasis and signal transduction in neurons. In the present study, we observed age-related changes in the ganglioside composition of synaptic plasma membranes. This led us to hypothesize that alterations in ganglioside species might contribute to the age-associated loss of PMCA activity. To probe the relationship between changes in endogenous ganglioside content or composition and PMCA activity in membranes of cortical neurons, we induced depletion of gangliosides by treating neurons with d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (d-PDMP). This caused a marked decrease in the activity of PMCA, which suggested a direct correlation between ganglioside content and PMCA activity. Neurons treated with neuraminidase exhibited an increase in GM1 content, a loss in poly-sialoganglioside content, and a decrease in PMCA activity that was greater than that produced by d-PDMP treatment. Thus, it appeared that poly-sialogangliosides had a stimulatory effect whereas mono-sialogangliosides had the opposite effect. Our observations add support to previous reports of PMCA regulation by gangliosides by demonstrating that manipulations of endogenous ganglioside content and species affect the activity of PMCA in neuronal membranes. Furthermore, our studies suggest that age-associated loss in PMCA activity may result in part from changes in the lipid environment of this Ca(2+) transporter. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Effects of Gangliosides on the Activity of the Plasma Membrane Ca2+-ATPase

    PubMed Central

    Jiang, Lei; Bechtel, Misty D.; Bean, Jennifer L.; Winefield, Robert; Williams, Todd D.; Zaidi, Asma; Michaelis, Elias K.; Michaelis, Mary L.

    2014-01-01

    Control of intracellular calcium concentrations ([Ca2+]i) is essential for neuronal function, and the plasma membrane Ca2+-ATPase (PMCA) is crucial for the maintenance of low [Ca2+]i. We previously reported on loss of PMCA activity in brain synaptic membranes during aging. Gangliosides are known to modulate Ca2+ homeostasis and signal transduction in neurons. In the present study, we observed age-related changes in the ganglioside composition of synaptic plasma membranes. This led us to hypothesize that alterations in ganglioside species might contribute to the age-associated loss of PMCA activity. To probe the relationship between changes in endogenous ganglioside content or composition and PMCA activity in membranes of cortical neurons, we induced depletion of gangliosides by treating neurons with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP). This caused a marked decrease in the activity of PMCA, which suggested a direct correlation between ganglioside content and PMCA activity. Neurons treated with neuraminidase exhibited an increase in GM1 content, a loss in poly-sialoganglioside content, and a decrease in PMCA activity that was greater than that produced by D-PDMP treatment. Thus, it appeared that poly-sialogangliosides had a stimulatory effect whereas mono-sialogangliosides had the opposite effect. Our observations add support to previous reports of PMCA regulation by gangliosides by demonstrating that manipulations of endogenous ganglioside content and species affect the activity of PMCA in neuronal membranes. Furthermore, our studies suggest that age-associated loss in PMCA activity may result in part from changes in the lipid environment of this Ca2+ transporter. PMID:24434060

  4. A first total synthesis of a hybrid-type ganglioside associated with amyotrophic lateral sclerosis-like disorder.

    PubMed

    Nakashima, Shinya; Ando, Hiromune; Imamura, Akihiro; Yuki, Nobuhiro; Ishida, Hideharu; Kiso, Makoto

    2011-01-10

    The hybrid ganglioside X1, which was identified in the bovine brain, was synthesized for the first time. Ganglioside X1 is believed to be involved in the development of amyotrophic lateral sclerosis-like disorders in patients with neurological disorders after treatment with bovine brain gangliosides. A convergent approach using two branched glycan units, the GM2-core trisaccharide and the lacto-ganglio tetrasaccharide, efficiently provided the highly branched heptasaccharide part of ganglioside X1, which was conjugated with the ceramide part to produce the protected ganglioside X1. Global deprotection delivered homogenous ganglioside X1, with which serum from the patient was reacted. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. BAFF aids generation of IgG anti-ganglioside antibodies in response to Campylobacter jejuni lipo-oligosaccharide.

    PubMed

    Matsumoto, Yukie; Kobata, Tetsuji; Odaka, Masaaki; Furukawa, Koichi; Hirata, Koichi; Yuki, Nobuhiro

    2010-01-25

    Ganglioside mimicry of Campylobacter jejuni lipo-oligosaccharide (LOS) can induce the production of IgG anti-ganglioside antibodies, but the generation mechanism has yet to be clarified. B-cell activating factor belonging to the TNF family (BAFF) helped murine B cells produce anti-ganglioside antibodies against C. jejuni LOS. In splenocyte culture, however, anti-ganglioside antibodies were produced in the presence of a soluble transmembrane activator and calcium-modulating and cyclophilin ligand interactor immunoadhesin (TACI-Ig), a receptor for BAFF. TACI-Ig adenoviral vectors failed to decrease production of anti-ganglioside antibodies in mice sensitized with C. jejuni LOS and did not alter IgG subclasses, evidence that BAFF aids but is not essential for the generation of IgG anti-ganglioside antibodies in response to C. jejuni LOS. Copyright 2009 Elsevier B.V. All rights reserved.

  6. Efficiently synthesizing lacto-ganglio-series gangliosides by using a glucosyl ceramide cassette approach: the total synthesis of ganglioside X2.

    PubMed

    Nakashima, Shinya; Ando, Hiromune; Saito, Risa; Tamai, Hideki; Ishida, Hideharu; Kiso, Makoto

    2012-05-01

    The first total synthesis of the hybrid ganglioside X2, which consisted of a highly branched octasaccharide and ceramide moieties, was accomplished by using a glucosyl ceramide cassette approach. With a disaccharyl donor, the heptasaccharide could not be constructed by glycosylation of the C4 hydroxy group of galactose at the reducing end of the pentasaccharide. In contrast, through an alternative approach with two branched glycan units, a GM2-core trisaccharide, and a lacto-ganglio tetrasaccharide, the heptasaccharyl donor could be prepared and subsequently joined with a glucosyl ceramide cassette to afford the protected ganglioside, X2. Finally, global deprotection completed the synthesis, thus affording the pure ganglioside X2. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Immunohistochemical detection of hepatic GM1 and GM2 gangliosides in streptozotocin-induced diabetic rats.

    PubMed

    Abregú, Adela V.; Genta, Susana B.; Sánchez Riera, Alicia N.; Sánchez, Sara S.

    2002-11-01

    This study was undertaken to investigate the consequences of diabetes on the expression of GM1 and GM2 gangliosides in rat liver. Experimental diabetes was induced by treatment with Streptozotocin (STZ) in adult male Sprague-Dawley rats. Two-dimensional thin-layer chromatography of total ganglioside preparations of liver tissues from STZ-induced diabetic rats showed an increased amount of GM1, while GM2 could not be detected. In order to identify ganglioside expression and corroborate possible changes after short-term diabetes (3 weeks), frozen sections of the liver were stained with two monoclonal antibodies, GMB16 (GM1 specific) and GMB28 (GM2 specific). Although both antibodies were capable of immunostaining the diabetic hepatocytes at the cell surface, strong reactivity was observed for GMB16 while GMB28 developed only a weak labeling. The hepatic ganglioside expression of insulin-stabilized diabetic rats was restored, resembling the profile of normal rats. The important alterations in the expression of GM1 and GM2 gangliosides in short-term diabetes were accompanied by certain microscopic changes in the liver, so that these gangliosides may be useful markers in the detection of early liver diabetic complications.

  8. Impaired Levels of Gangliosides in the Corpus Callosum of Huntington Disease Animal Models

    PubMed Central

    Di Pardo, Alba; Amico, Enrico; Maglione, Vittorio

    2016-01-01

    Huntington Disease (HD) is a genetic neurodegenerative disorder characterized by broad types of cellular and molecular dysfunctions that may affect both neuronal and non-neuronal cell populations. Among all the molecular mechanisms underlying the complex pathogenesis of the disease, alteration of sphingolipids has been identified as one of the most important determinants in the last years. In the present study, besides the purpose of further confirming the evidence of perturbed metabolism of gangliosides GM1, GD1a, and GT1b the most abundant cerebral glycosphingolipids, in the striatal and cortical tissues of HD transgenic mice, we aimed to test the hypothesis that abnormal levels of these lipids may be found also in the corpus callosum white matter, a ganglioside-enriched brain region described being dysfunctional early in the disease. Semi-quantitative analysis of GM1, GD1a, and GT1b content indicated that ganglioside metabolism is a common feature in two different HD animal models (YAC128 and R6/2 mice) and importantly, demonstrated that levels of these gangliosides were significantly reduced in the corpus callosum white matter of both models starting from the early stages of the disease. Besides corroborating the evidence of aberrant ganglioside metabolism in HD, here, we found out for the first time, that ganglioside dysfunction is an early event in HD models and it may potentially represent a critical molecular change influencing the pathogenesis of the disease. PMID:27766070

  9. The Protective Effect of Gangliosides on Lead (Pb)-Induced Neurotoxicity Is Mediated by Autophagic Pathways

    PubMed Central

    Meng, Hongtao; Wang, Lan; He, Junhong; Wang, Zhufeng

    2016-01-01

    Lead (Pb) is a ubiquitous environmental and industrial pollutant and can affect intelligence development and the learning ability and memory of children. Therefore, necessary measures should be taken to protect the central nervous system (CNS) from Pb toxicity. Gangliosides are sialic acid-containing glycosphingolipids that are constituents of mammalian cell membranes and are more abundantly expressed in the CNS. Studies have shown that gangliosides constitute a useful tool in the attempt to promote functional recovery of CNS and can reverse Pb-induced impairments of synaptic plasticity in rats. However, the detailed mechanisms have yet to be fully understood. In our present study, we tried to investigate the role of gangliosides in Pb-induced injury in hippocampus neurons and to further confirm the detailed mechanism. Our results show that Pb-induced injuries in the spatial reference memory were associated with a reduction of cell viability and cell apoptosis, and treatment with gangliosides markedly ameliorated the Pb-induced injury by inhibition of apoptosis action. Gangliosides further attenuated Pb-induced the abnormal autophagic process by regulation of mTOR pathways. In summary, our study establishes the efficacy of gangliosides as neuroprotective agents and provides a strong rationale for further studies on the underlying mechanisms of their neuroprotective functions. PMID:27023584

  10. Occurrence and tissue distribution of c-series gangliosides in the common squid Todarodes pacificus.

    PubMed

    Saito, Megumi; Kitamura, Hisayo; Sugiyama, Kiyoshi

    2002-03-01

    We have recently demonstrated that the common squid Todarodes pacificus express acidic lipids that were reactive with a monoclonal antibody A2B5. In the present study, two A2B5-reactive acidic lipids were isolated from squid hepatopancreatic tissue and characterized for their structures by methods including glycolipid overlay analysis, product analysis after sialidase treatment, and electrospray ionization-mass spectrometry (ESI-MS). Accordingly, the two acidic lipid were identified as GT3 and GQ1c, respectively. Another A2B5-reactive acidic lipid in the tissue was tentatively assigned to GT2 based upon its reactivity to A2B5 and chromatographic mobility on thin-layer chromatography. The composition and concentration of c-series gangliosides significantly differed among squid tissues (i.e. hepatopancreas, cerebral ganglion, eye lens, and mantle tissue). Interestingly, the percentages of c-series gangliosides within total gangliosides of hepatopancreas and cerebral ganglion were even higher than that of cod fish brain, which is known to be highly enriched with this ganglioside species. These findings strongly support the hypothesis that c-series gangliosides in squid tissues are not derived from ganglioside-containing food intake, but biosynthesized in a tissue-specific manner.

  11. Immunolocalization of GQ1b and related gangliosides in human extraocular neuromuscular junctions and muscle spindles.

    PubMed

    Liu, Jing-Xia; Willison, Hugh J; Pedrosa-Domellöf, Fatima

    2009-07-01

    To examine the distribution of anti-GQ1b, -GT1a, and -GD1b antibody binding in human extraocular muscles (EOMs), axial and limb muscles, and muscle spindles and thereby test the hypothesis that their distinctive ganglioside composition provides the molecular basis for selective involvement of EOMs and muscle spindles in Miller Fisher syndrome. Muscle samples from adult human EOMs, vastus lateralis, biceps brachii, lumbrical, psoas, and deep muscles of the neck were processed for immunohistochemistry, with monoclonal antibodies against ganglioside GQ1b, GT1a, and GD1b. Neuromuscular junctions (NMJs) were detected by alpha-bungarotoxin binding and by acetyl cholinesterase reaction. Most motor endplates of human EOMs richly bound anti-GQ1b, -GT1a, and -GD1b ganglioside antibodies. Anti-GQ1b, -GT1a, and -GD1b ganglioside antibody bindings to NMJs in human limb and axial muscle were scarce, but the nerve terminals inside muscle spindles and in direct contact with intrafusal fibers were labeled with anti- GQ1b, -GT1a, and -GD1b ganglioside antibodies. The abundant and synaptic-specific binding of anti-GQ1b, -GT1a, and -GD1b ganglioside antibodies and the rich capillary supply in the human EOMs may partly explain the selective paralysis of these muscles in Miller Fisher syndrome.

  12. Variability in brain ganglioside content and composition of endothermic mammals, heterothermic hibernators and ectothermic fishes.

    PubMed

    Kappel, T; Hilbig, R; Rahmann, H

    1993-06-01

    Content and composition of brain gangliosides were compared among endothermic mammals, heterothermic hibernators and ectothermic fishes from habitats with extreme ambient temperatures (tropic vs. antarctic waters). In general the content of brain gangliosides in fishes is significantly lower and exhibits a greater variability than in mammals. The composition of brain gangliosides was investigated using both one- and two-dimensional High Performance Thin Layer Chromatography (HPTLC). Both techniques showed a remarkable increase in the number of individual ganglioside fractions and an additional increase of higher polar fractions in fishes as compared with mammals. The 2D-HPTLC revealed a significant decrease in the relative proportion of alkali-labile gangliosides in the course of evolution from fish to mammals. Moreover this decrease in alkali-lability is correlated with the state of thermal adaptation (antarctic fishes, 53-66%; tropical cichlid fish, 35%). These results provide additional evidence for the notion that the extremely high polarity of brain gangliosides, especially of cold-blooded vertebrates, reflects a very efficient mechanism on the molecular level to keep the neuronal membrane functional under low temperature conditions.

  13. The Protective Effect of Gangliosides on Lead (Pb)-Induced Neurotoxicity Is Mediated by Autophagic Pathways.

    PubMed

    Meng, Hongtao; Wang, Lan; He, Junhong; Wang, Zhufeng

    2016-03-25

    Lead (Pb) is a ubiquitous environmental and industrial pollutant and can affect intelligence development and the learning ability and memory of children. Therefore, necessary measures should be taken to protect the central nervous system (CNS) from Pb toxicity. Gangliosides are sialic acid-containing glycosphingolipids that are constituents of mammalian cell membranes and are more abundantly expressed in the CNS. Studies have shown that gangliosides constitute a useful tool in the attempt to promote functional recovery of CNS and can reverse Pb-induced impairments of synaptic plasticity in rats. However, the detailed mechanisms have yet to be fully understood. In our present study, we tried to investigate the role of gangliosides in Pb-induced injury in hippocampus neurons and to further confirm the detailed mechanism. Our results show that Pb-induced injuries in the spatial reference memory were associated with a reduction of cell viability and cell apoptosis, and treatment with gangliosides markedly ameliorated the Pb-induced injury by inhibition of apoptosis action. Gangliosides further attenuated Pb-induced the abnormal autophagic process by regulation of mTOR pathways. In summary, our study establishes the efficacy of gangliosides as neuroprotective agents and provides a strong rationale for further studies on the underlying mechanisms of their neuroprotective functions.

  14. Imaging mass spectrometry identifies prognostic ganglioside species in rodent intracranial transplants of glioma and medulloblastoma.

    PubMed

    Ermini, Leonardo; Morganti, Elena; Post, Alexander; Yeganeh, Behzad; Caniggia, Isabella; Leadley, Michael; Faria, Claudia C; Rutka, James T; Post, Martin

    2017-01-01

    Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (MALDI-MSI) allows us to investigate the distribution of lipid molecules within tissues. We used MALDI-MSI to identify prognostic gangliosides in tissue sections of rat intracranial allografts of rat glioma and mouse intracranial xenografts of human medulloblastoma. In the healthy adult rodent brain, GM1 and GD1 were the main types of glycolipids. Both gangliosides were absent in both intracranial transplants. The ganglioside GM3 was not present in the healthy adult brain but was highly expressed in rat glioma allografts. In combination with tandem mass spectrometry GM3 (d18:1/C24:0) was identified as the most abundant ganglioside species in the glioma allotransplant. By contrast, mouse xenografts of human medulloblastoma were characterized by prominent expression of the ganglioside GM2 (d18:0/C18:0). Together, these data demonstrate that tissue-based MALDI-MSI of gangliosides is able to discriminate between different brain tumors and may be a useful clinical tool for their classification and grading.

  15. Are anti-ganglioside antibodies associated with proventricular dilatation disease in birds?

    PubMed

    Leal de Araujo, Jeann; Tizard, Ian; Guo, Jianhua; Heatley, J Jill; Rodrigues Hoffmann, Aline; Rech, Raquel R

    2017-01-01

    The identification of Parrot bornaviruses (PaBV) in psittacine birds with proventricular dilatation disease (PDD) has not been sufficient to explain the pathogenesis of this fatal disease, since not all infected birds develop clinical signs. Although the most accepted theory indicates that PaBV directly triggers an inflammatory response in this disease, another hypothesis suggests the disease is triggered by autoantibodies targeting neuronal gangliosides, and PDD might therefore resemble Guillain-Barré Syndrome (GBS) in its pathogenesis. Experimental inoculation of pure gangliosides and brain-derived ganglioside extracts were used in two different immunization studies. The first study was performed on 17 healthy chickens (Gallus gallus domesticus): 11 chickens were inoculated with a brain ganglioside extract in Freund's complete adjuvant (FCA) and six chickens inoculated with phosphate-buffered saline. A second study was performed five healthy quaker parrots (Myiopsitta monachus) that were divided into three groups: Two quaker parrots received purified gangliosides in FCA, two received a crude brain extract in FCA, and one control quaker parrot received FCA alone. One chicken developed difficult in walking. Histologically, only a mild perivascular and perineural lymphocytic infiltrate in the proventriculus. Two quaker parrots (one from each treatment group) had mild lymphoplasmacytic encephalitis and myelitis. However, none of the quaker parrots developed myenteric ganglioneuritis, suggesting that autoantibodies against gangliosides in birds are not associated with a condition resembling PDD.

  16. Are anti-ganglioside antibodies associated with proventricular dilatation disease in birds?

    PubMed Central

    Tizard, Ian; Guo, Jianhua; Heatley, J Jill; Rodrigues Hoffmann, Aline

    2017-01-01

    The identification of Parrot bornaviruses (PaBV) in psittacine birds with proventricular dilatation disease (PDD) has not been sufficient to explain the pathogenesis of this fatal disease, since not all infected birds develop clinical signs. Although the most accepted theory indicates that PaBV directly triggers an inflammatory response in this disease, another hypothesis suggests the disease is triggered by autoantibodies targeting neuronal gangliosides, and PDD might therefore resemble Guillain-Barré Syndrome (GBS) in its pathogenesis. Experimental inoculation of pure gangliosides and brain-derived ganglioside extracts were used in two different immunization studies. The first study was performed on 17 healthy chickens (Gallus gallus domesticus): 11 chickens were inoculated with a brain ganglioside extract in Freund’s complete adjuvant (FCA) and six chickens inoculated with phosphate-buffered saline. A second study was performed five healthy quaker parrots (Myiopsitta monachus) that were divided into three groups: Two quaker parrots received purified gangliosides in FCA, two received a crude brain extract in FCA, and one control quaker parrot received FCA alone. One chicken developed difficult in walking. Histologically, only a mild perivascular and perineural lymphocytic infiltrate in the proventriculus. Two quaker parrots (one from each treatment group) had mild lymphoplasmacytic encephalitis and myelitis. However, none of the quaker parrots developed myenteric ganglioneuritis, suggesting that autoantibodies against gangliosides in birds are not associated with a condition resembling PDD. PMID:28413724

  17. Cloning and transcriptional regulation of genes responsible for synthesis of gangliosides.

    PubMed

    Zeng, Guichao; Yu, Robert K

    2008-04-01

    Ganglioside synthases are glycosyltransferases involved in the biosynthesis of glycoconjugates. A number of ganglioside synthase genes have been cloned and characterized. They are classified into different families of glycosyltransferases based on similarities of their amino acid sequences. Tissue-specific expression of these genes has been analyzed by hybridization using cDNA fragments. Enzymatic characterization with the expressed recombinant enzymes showed these enzymes differ in their donor and acceptor substrate specificities and other biochemical parameters. In vitro enzymatic analysis also showed that one linkage can be synthesized by multiple enzymes and one enzyme may be responsible for synthesis of multiple gangliosides. Following the cloning of the ganglioside synthase genes, the promoters of the key synthase genes in the ganglioside biosynthetic pathway have been cloned and analyzed. All of the promoters are TATA-less, lacking a CCAAT box but containing GC-rich boxes, characteristic of the house-keeping genes, although transcription of ganglioside synthase genes is subject to complex developmental and tissue-specific regulation. A set of cis-acting elements and transcription factors, including Sp1, AP2, and CREB, function in the proximal promoters. Negative-regulatory regions have also been defined in most of the promoters. We present here an overview of these genes and their transcriptional regulation.

  18. A comparative study on ceramide composition of cetacean brain gangliosides.

    PubMed

    Terabayashi, T; Ogawa, T; Kawanishi, Y

    1992-11-01

    1. Ceramide composition and N-glycolylneuraminic acid content of gangliosides from gray and white matters and myelin of cerebrum and cerebellum were analyzed in eight species belonging to the suborder Odontoceti and two species to Mystacoceti. 2. The most characteristic feature was high contents of C20:0 (10-40%) and C24 species (5-40%). 3. Content of hydroxy fatty acid of C24 species was higher in cerebellum (5-20%) than cerebrum (0-3%). 4. Major component of long-chain base was dC18:1 (70-90%). 5. N-glycolylneuraminic acid was found in sperm whale, Dall's porpoise and killer whale (0.1-1.7%).

  19. Configuration and interactions of the polar head group in gangliosides

    PubMed Central

    Maggio, Bruno; Cumar, Federico A.; Caputto, Ranwel

    1980-01-01

    1. The interactions of gangliosides with Ca2+ and some polar-head-group requirements for establishment of particular interactions with phosphatidylcholine were studied in monolayers at the air/145mm-NaCl interface. 2. Ganglioside–Ca2+ interactions, as revealed by surface-potential measurements, depended on the position occupied by sialosyl residues in the oligosaccharide chain. The interactions with Ca2+ of the single sialosyl residue of monosialogangliosides occurred above 0.1mm-CaCl2, whereas the interaction of the cation with additional sialosyl groups in di- or tri-sialogangliosides depended on the carbohydrate residue to which the sialosyl moiety was attached. The sialosyl residue bound in sialosyl–sialosyl linkage interacted very little with Ca2+. The sialosyl residue attached to the terminal galactose of the neutral tetrasaccharide chain interacted with Ca2+ above 1μm-CaCl2. 3. Experiments with mixed monolayers containing dihexadecyl phosphate and hexadecyltrimethylammonium indicated that for the occurrence of interactions of polysialogangliosides with phosphatidylcholine characterized by reductions in molecular packing and surface potential both charged groups of the phospholipid and sialosyl residues with particular dipolar properties in the ganglioside are participating. 4. Possible configurations that can explain the behaviour in monolayers were inspected with space-filling molecular models. The position of the carboxylate group of sialosyl residues with respect to the interface and to the sialosyl molecular plane can explain the different orientation of the dipole-moment vector of this residue, which depends on the position to which it is linked in the oligosaccharide chain. Favoured interactions of polysialogangliosides with phosphatidylcholine may result from a configuration allowing a partial matching of two oppositely oriented electrical vectors contributed by the zwitterionic phosphocholine group and particular sialosyl groups. ImagesPLATE 1

  20. Alpha-fucosidase-ganglioside interactions. Action of alpha-L-fucosidase from the hepatopancreas of Octopus vulgaris on a fucose-containing ganglioside (Fuc-GM1).

    PubMed Central

    Masserini, M; Giuliani, A; Venerando, B; Fiorilli, A; D'Aniello, A; Tettamanti, G

    1985-01-01

    alpha-L-Fucosidase, prepared in highly purified form (Mr 70 000-74 000) from Octopus hepatopancreas, was able to hydrolyse a fucose-containing ganglioside, namely Fuc-GM1 (II3NeuAc,IV2Fuc-GgOse4-Cer). The enzyme showed an irregular kinetic behaviour (v/[S] and v/[E] relationships following sigmoidal curves) when working on micellar Fuc-GM1 (Mr of the micelle 500 000), but obeyed regular hyperbolic kinetics when acting on low-Mr substances. It was observed that, on incubation with micellar Fuc-GM1 under the conditions used for the enzyme assay, Octopus alpha-L-fucosidase produced a ganglioside-enzyme complex that was catalytically inactive. This complex had an Mr exceeding 500 000 and a ganglioside/protein ratio of 4:1 (w/w), which is consistent with a stoichiometric combination of one ganglioside micelle with two enzyme molecules. Inactivation of alpha-L-fucosidase by formation of the corresponding complexes was also obtained with micellar gangliosides GM1 (II3NeuAc-GgOse4-Cer), GD1a (II3NeuAc,IV3NeuAc-GgOse4-Cer) and GT1b [II3(NeuAc)2,IV3-NeuAc-GgOse4-Cer], which are not substrates for the enzyme, indicating that the ganglioside micelles per se act as enzyme inhibitors. However, alpha-L-fucosidase easily forms a Fuc-GM1-alpha-L-fucosidase complex, displaying regular Michaelis-Menten kinetics. Therefore the anomalous behaviour exhibited by alpha-L-fucosidase on micellar Fuc-GM1 is likely due to formation of the complex, which separates the fucosyl linkage from the active site of the complexed enzyme, but makes it available to the enzyme in the free form. Images Fig. 2. Fig. 9. PMID:4052012

  1. Alpha-fucosidase-ganglioside interactions. Action of alpha-L-fucosidase from the hepatopancreas of Octopus vulgaris on a fucose-containing ganglioside (Fuc-GM1).

    PubMed

    Masserini, M; Giuliani, A; Venerando, B; Fiorilli, A; D'Aniello, A; Tettamanti, G

    1985-08-01

    alpha-L-Fucosidase, prepared in highly purified form (Mr 70 000-74 000) from Octopus hepatopancreas, was able to hydrolyse a fucose-containing ganglioside, namely Fuc-GM1 (II3NeuAc,IV2Fuc-GgOse4-Cer). The enzyme showed an irregular kinetic behaviour (v/[S] and v/[E] relationships following sigmoidal curves) when working on micellar Fuc-GM1 (Mr of the micelle 500 000), but obeyed regular hyperbolic kinetics when acting on low-Mr substances. It was observed that, on incubation with micellar Fuc-GM1 under the conditions used for the enzyme assay, Octopus alpha-L-fucosidase produced a ganglioside-enzyme complex that was catalytically inactive. This complex had an Mr exceeding 500 000 and a ganglioside/protein ratio of 4:1 (w/w), which is consistent with a stoichiometric combination of one ganglioside micelle with two enzyme molecules. Inactivation of alpha-L-fucosidase by formation of the corresponding complexes was also obtained with micellar gangliosides GM1 (II3NeuAc-GgOse4-Cer), GD1a (II3NeuAc,IV3NeuAc-GgOse4-Cer) and GT1b [II3(NeuAc)2,IV3-NeuAc-GgOse4-Cer], which are not substrates for the enzyme, indicating that the ganglioside micelles per se act as enzyme inhibitors. However, alpha-L-fucosidase easily forms a Fuc-GM1-alpha-L-fucosidase complex, displaying regular Michaelis-Menten kinetics. Therefore the anomalous behaviour exhibited by alpha-L-fucosidase on micellar Fuc-GM1 is likely due to formation of the complex, which separates the fucosyl linkage from the active site of the complexed enzyme, but makes it available to the enzyme in the free form.

  2. Study on the Grain Refinement Behavior of Mg-Zr Master Alloy and Zr Containing Compounds in Mg-10Gd-3Y Magnesium Alloy

    NASA Astrophysics Data System (ADS)

    Wu, Guohua; Sun, Ming; Dai, Jichun; Ding, Wenjiang

    The effects of Mg-Zr master alloy and a potassium fluozirconate (K2ZrF6) salt mixture (KSM) on the grain refinement behavior of Mg-10Gd-3Y magnesium alloy were studied. The results show that the Mg-10Gd-3Y alloy is well refined by Mg-Zr or KSM. The characteristic micro structure feature of the alloy refined by Mg-Zr master alloy is the Zr-rich cores that exist in most grains, while the Zr-rich cores are not observed in the alloy refined by KSM. It is suggested that the grain refinement mechanisms of zirconium in the two cases are different: the Zr released from Mg-Zr master alloy works by adding heterogeneous nucleants, while the Zr produced from the in-situ reaction between Mg melt and K2ZrF6 works by restricting grain growth. Compared with the Mg-30.wt%Zr master alloy, the KSM refiner shows much longer fading time during melting.

  3. Ultraviolet-light-emitting AlN:Gd thin-film electroluminescence device using an energy transfer from Gd3+ ions to N2 molecules

    NASA Astrophysics Data System (ADS)

    Toyama, Toshihiko; Ota, Jun; Adachi, Daisuke; Niioka, Yasumasa; Lee, Dong-Hun; Okamoto, Hiroaki

    2009-04-01

    An ultraviolet (UV)-light-emitting AlN:Gd thin-film electroluminescence device (TFELD) was demonstrated for application to flat-panel lighting. AlN:Gd thin films were deposited by rf magnetron sputtering at 200 °C and applied to an ac-voltage-driven TFELD with a double-insulating structure as an emission layer. UV-light emission was observed over a threshold voltage of 270 V for a 5 kHz sinusoidal ac voltage. Electroluminescence (EL) spectra were compared with photoluminescence and cathodoluminescence spectra of AlN:Gd originating from Gd3+ P6j→S87/2 transitions and with an emission spectrum of the second positive system (C3Πu→B3Πg) of N2 molecules. As a result, an energy transfer from Gd3+ P6j→S87/2 to N2 C3Πu→B3Πg is discussed as a likely mechanism for the UV EL. Finally, a preliminary result, associated with the conversion from UV light into blue-green light via a phosphor, is demonstrated for the color tunability of the TFELD.

  4. Effect of partially replacement of Gd3+ ions on fluorescence properties of YBO3:Eu3+ phosphor synthesized via precipitation method

    NASA Astrophysics Data System (ADS)

    Koparkar, K. A.; Bajaj, N. S.; Omanwar, S. K.

    2015-01-01

    The series of (Y(1-x)Gdx)BO3:0.01Eu3+ phosphors was successfully synthesized by precipitation method. All phosphors were characterized by X-ray diffraction pattern (XRD) for crystalline structure and UV-vis, photoluminescence (PL) and decay curves measurements were carried out to characterize their optical properties. The PL emission spectra of (Y(1-x)Gdx)BO3:0.01Eu3+ phosphors indicated that red-orange (595 nm) color could be well excited by 233 nm. The effect of x (Gd3+ ions) increases in (Y(1-x)Gdx)BO3:0.01Eu3+ on PL properties has been examined. The results showed that increment of x molar concentration in (Y(1-x)Gdx)BO3:0.01Eu3+ would lead to a outstanding enhancement of fluorescence intensity. The chromaticity coordinates (CIE) were calculated. The R/O ratio of the luminescence intensity of 5D0 → 7F2 (red) to 5D0 → 7F1 (orange) transitions were very well increases with the increasing percentage of Gd3+ ions in (Y(1-x)Gdx)BO3:0.01Eu3+ phosphor.

  5. Effect of Gd3+ substitution on the structural and electrical properties of Mg0.75Zn0.25Fe2O4 nanoparticles

    NASA Astrophysics Data System (ADS)

    Sebastian, R. M.; Mohammed, E. M.

    2016-12-01

    Nanoparticles of gadolinium substituted Mg-Zn ferrite, Mg0.75Zn0.25GdxFe2-xO4 (where x = 0.00, 0.05, 0.10, 0.15) have been prepared by the sol-gel technique. The lattice constant is found to increase with increase in the Gd3+ ion concentration. The observed variation of dielectric constant with frequency is explained on the basis of the Maxwell-Wagner two layer model and the electron hopping mechanism. The dielectric constant and dielectric loss decrease with Gd3+ ion substitution. The variation of AC conductivity with frequency suggests that the conduction is due to small polaron hopping. It is also noticed that the dielectric constant and the AC conductivity increase with temperature and it is explained in terms of the thermally enhanced drift mobility of the charge carriers. The observed low value of dielectric constant and also the dielectric loss factor obtained for gadolinium substituted ferrites make them desirable for high frequency applications.

  6. 5 7 Fe Emission Mössbauer Study on Gd 3 Ga 5 O 1 2 implanted with dilute 5 7 Mn

    NASA Astrophysics Data System (ADS)

    Krastev, P. B.; Gunnlaugsson, H. P.; Nomura, K.; Adoons, V.; Gerami, A. M.; Johnston, K.; Ncube, M.; Mantovan, R.; Masenda, H.; Matveyev, Y. A.; Mølholt, T. E.; Unzueta, I.; Bharuth-Ram, K.; Gislason, H.; Langouche, G.; Naidoo, D.; Ólafsson, S.

    2016-12-01

    57Fe emission Mössbauer spectroscopy has been applied to study the lattice location and properties of Fe in gadolinium gallium garnet Gd3Ga5 O 12 (GGG) single crystals in the temperature interval 300 - 563 K within the extremely dilute (<10-4 at.%) regime following the implantation of57Mn ( T 1 / 2= 1.5 min.) at ISOLDE/CERN. These results are compared with earlier Mössbauer spectroscopy study of Fe-doped gadolinium gallium garnet Gd3Ga5 O 12(GGG), with implantation fluences between 8×1015 and 6×1016 atoms cm-2. Three Fe components are observed in the emission Mössbauer spectra: (i) high spin Fe2+ located at damage sites due to the implantation process, (ii) high spin Fe3+ at substitutional tetrahedral Ga sites, and (iii) interstitial Fe, probably due to the recoil imparted on the daughter57∗Fe nucleus in the β - decay of57Mn. In contrast to high fluence57Fe implantation studies the Fe3+ ions are found to prefer the tetrahedral Ga site over the octahedral Ga site. No annealing stages are evident in the temperature range investigated. Despite the very low concentration, high-spin Fe3+ shows fast spin relaxation, presumably due to an indirect interaction between nearby gadolinium atoms.

  7. Investigation of cyano-bridged coordination nanoparticles Gd3+/[Fe(CN)6]3-/d-mannitol as T1-weighted MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Perrier, M.; Gallud, A.; Ayadi, A.; Kennouche, S.; Porredon, C.; Gary-Bobo, M.; Larionova, J.; Goze-Bac, Ch.; Zanca, M.; Garcia, M.; Basile, I.; Long, J.; de Lapuente, J.; Borras, M.; Guari, Y.

    2015-07-01

    Cyano-bridged Gd3+/[Fe(CN)6]3- coordination polymer nanoparticles of 3-4 nm stabilized with d-mannitol presenting a high r1 relaxivity value of 11.4 mM-1 s-1 were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity.Cyano-bridged Gd3+/[Fe(CN)6]3- coordination polymer nanoparticles of 3-4 nm stabilized with d-mannitol presenting a high r1 relaxivity value of 11.4 mM-1 s-1 were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity. Electronic supplementary information (ESI) available: Experimental details and procedures, toxicological data, physical characterization. See DOI: 10.1039/c5nr01557j

  8. Role of Ce4+ in the Scintillation Mechanism of Codoped Gd3Ga3Al2O12∶Ce

    NASA Astrophysics Data System (ADS)

    Wu, Yuntao; Meng, Fang; Li, Qi; Koschan, Merry; Melcher, Charles L.

    2014-10-01

    To control the time-response performance of widely used cerium-activated scintillators in cutting-edge medical-imaging devices, such as time-of-flight positron-emission tomography, a comprehensive understanding of the role of Ce valence states, especially stable Ce44, in the scintillation mechanism is essential. However, despite some progress made recently, an understanding of the physical processes involving Ce4+ is still lacking. The aim of this work is to clarify the role of Ce4+ in scintillators by studying Ca2+ codoped Gd3Ga3Al2O12∶Ce (GGAG ∶Ce). By using a combination of optical absorption spectra and x-ray absorption near-edge spectroscopies, the correlation between Ca2+ codoping content and the Ce4+ fraction is seen. The energy-level diagrams of Ce3+ and Ce4+ in the Gd3Ga3Al2O12 host are established by using theoretical and experimental methods, which indicate a higher position of the 5d1 state of Ce4+ in the forbidden gap in comparison to that of Ce3+. Underlying reasons for the decay-time acceleration resulting from Ca2+ codoping are revealed, and the physical processes of the Ce4+-emission model are proposed and further demonstrated by temperature-dependent radioluminescence spectra under x-ray excitation.

  9. Effect of Mg2+ ions co-doping on luminescence and defects formation processes in Gd3(Ga,Al)5O12:Ce single crystals

    NASA Astrophysics Data System (ADS)

    Babin, V.; Bohacek, P.; Grigorjeva, L.; Kučera, M.; Nikl, M.; Zazubovich, S.; Zolotarjovs, A.

    2017-04-01

    Photo- and radioluminescence and thermally stimulated luminescence characteristics of Ce3+ - doped and Ce3+, Mg2+ co-doped Gd3(Ga,Al)5O12 (GAGG) single crystals of similar composition are investigated in the 9-500 K temperature range. The Ce3+ - related luminescence spectra and the photoluminescence decay kinetics in these crystals are found to be similar. Under photoexcitation in the Ce3+ - and Gd3+ - related absorption bands, no prominent rise of the photoluminescence intensity in time is observed neither in GAGG:Ce,Mg nor in GAGG:Ce crystals. The afterglow is strongly reduced in GAGG:Ce,Mg as compared to GAGG:Ce, and the afterglow decay kinetics is much faster. Co-doping with Mg2+ results in a drastic decrease of the thermally stimulated luminescence (TSL) intensity in the whole investigated temperature range and in the appearance of a new complex Mg2+ - related TSL glow curve peak around 285 K. After irradiation in the Ce3+ - related 3.6 eV absorption band, the TSL intensity in GAGG:Ce,Mg is found to be comparable with that in the GAGG:Ce epitaxial film of similar composition. The Mg2+ - induced changes in the concentration, origin and structure of the crystal lattice defects and their influence on the scintillation characteristics of GAGG:Ce,Mg are discussed.

  10. Temperature dependences of the parameters of the initial splitting of Gd3+ in CaMoO4 (lattice and spin-phonon contributions)

    NASA Astrophysics Data System (ADS)

    Gorlov, A. D.

    2017-03-01

    The electron paramagnetic resonance (EPR) spectra of Gd3+ impurity centers in CaMoO4 single crystals have been investigated at temperatures T = 1.8, 4.2, and 99-300 K. The temperature dependences of the spin Hamiltonian parameters bn m( T) ( n = 2, 4, m = 0, 4) have been determined, and their analysis has been carried out. The temperature contributions from the static lattice, b 2(L) and b 4m(L), to the spin Hamiltonian parameters b n m( T) have been separated. For this purpose, the changes of the static lattice contributions b 2(L) and b 4m(L) have been determined taking into account the temperature shifts of the oxygen ions nearest to the Gd3+ ions in CaMoO4 single crystals. The differences b nm( F) = bn m- b nm(L) have been attributed to the spin-phonon contribution. The analysis of the results obtained has demonstrated that the parameters b 20( F) and b 4m( F) are positive, and the dependence of b 20( F) on the temperature T is well described in the model of local vibrations (G. Pfister). However, the temperature behavior of the parameter b 4m(F) could not be described in the framework of the well-known models of the spin-phonon interaction.

  11. Charge deformation and orbital hybridization: intrinsic mechanisms on tunable chromaticity of Y3Al5O12:Ce3+ luminescence by doping Gd3+ for warm white LEDs

    PubMed Central

    Chen, Lei; Chen, Xiuling; Liu, Fayong; Chen, Haohong; Wang, Hui; Zhao, Erlong; Jiang, Yang; Chan, Ting-Shan; Wang, Chia-Hsin; Zhang, Wenhua; Wang, Yu; Chen, Shifu

    2015-01-01

    The deficiency of Y3Al5O12:Ce (YAG:Ce) luminescence in red component can be compensated by doping Gd3+, thus lead to it being widely used for packaging warm white light-emitting diode devices. This article presents a systematic study on the photoluminescence properties, crystal structures and electronic band structures of (Y1−xGdx)3Al5O12: Ce3+ using powerful experimental techniques of thermally stimulated luminescence, X-ray diffraction, X-ray absorption near edge structure (XANES), extended X-ray absorption fine structure (EXAFS) and ultraviolet photoelectron spectra (UPS) of the valence band, assisted with theoretical calculations on the band structure, density of states (DOS), and charge deformation density (CDD). A new interpretation from the viewpoint of compression deformation of electron cloud in a rigid structure by combining orbital hybridization with solid-state energy band theory together is put forward to illustrate the intrinsic mechanisms that cause the emission spectral shift, thermal quenching, and luminescence intensity decrease of YAG: Ce upon substitution of Y3+ by Gd3+, which are out of the explanation of the classic configuration coordinate model. The results indicate that in a rigid structure, the charge deformation provides an efficient way to tune chromaticity, but the band gaps and crystal defects must be controlled by comprehensively accounting for luminescence thermal stability and efficiency. PMID:26175141

  12. Charge deformation and orbital hybridization: intrinsic mechanisms on tunable chromaticity of Y3Al5O12:Ce3+ luminescence by doping Gd3+ for warm white LEDs.

    PubMed

    Chen, Lei; Chen, Xiuling; Liu, Fayong; Chen, Haohong; Wang, Hui; Zhao, Erlong; Jiang, Yang; Chan, Ting-Shan; Wang, Chia-Hsin; Zhang, Wenhua; Wang, Yu; Chen, Shifu

    2015-07-15

    The deficiency of Y3Al5O12:Ce (YAG:Ce) luminescence in red component can be compensated by doping Gd(3+), thus lead to it being widely used for packaging warm white light-emitting diode devices. This article presents a systematic study on the photoluminescence properties, crystal structures and electronic band structures of (Y1-xGdx)3Al5O12: Ce(3+) using powerful experimental techniques of thermally stimulated luminescence, X-ray diffraction, X-ray absorption near edge structure (XANES), extended X-ray absorption fine structure (EXAFS) and ultraviolet photoelectron spectra (UPS) of the valence band, assisted with theoretical calculations on the band structure, density of states (DOS), and charge deformation density (CDD). A new interpretation from the viewpoint of compression deformation of electron cloud in a rigid structure by combining orbital hybridization with solid-state energy band theory together is put forward to illustrate the intrinsic mechanisms that cause the emission spectral shift, thermal quenching, and luminescence intensity decrease of YAG: Ce upon substitution of Y(3+) by Gd(3+), which are out of the explanation of the classic configuration coordinate model. The results indicate that in a rigid structure, the charge deformation provides an efficient way to tune chromaticity, but the band gaps and crystal defects must be controlled by comprehensively accounting for luminescence thermal stability and efficiency.

  13. Explanation for the variance of the Ce 3+ emission energy in LnI 3 [Ln = Lu 3+, Y 3+, Gd 3+

    NASA Astrophysics Data System (ADS)

    Srivastava, A. M.; Camardello, S. J.; Comanzo, H. A.; Aycibin, M.; Happek, U.

    2010-07-01

    The experimental result that the energy of the emitted photon increases with decreasing ionic radii of the host lattice is a remarkable feature of the Ce 3+ luminescence in the isostructural LnI 3 [Ln 3+ = Lu 3+, Y 3+, Gd 3+] family of materials. To understand this variation, the optical properties of YI 3:Ce 3+ is measured and compared with those reported for Ce 3+ activated LuI 3 and GdI 3. The results indicate that the crystal field splitting and the centroid shift of the Ce 3+ 5d 1 electronic configuration in these iodides are of the same order of magnitude. The lowest energy Ce 3+ 4f 1 → 5d 1 excitation transition in LnI 3 [Ln 3+ = Lu 3+, Y 3+, Gd 3+] is practically uninfluenced by the ionic radii of the host lattice cation, which the Ce 3+ ion substitutionally replaces. The increase in energy of the emitted photon with decreasing ionic radii of the host lattice is a result of the increasing Stokes shift of the Ce 3+ emission in the sequence LuI 3-YI 3-GdI 3. The quenching temperature of the Ce 3+ emission in YI 3 is high.

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

    PubMed Central

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

    2016-01-01

    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 extraction 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 analysis of gangliosides in negative ion mode. In addition, the pretreatment by ethanol (EtOH) cleaning brain section and the addition of ammonium formate greatly improved the MS signal of gangliosides in the brain section when MALDI MSI analysis was employed. The distribution of ganliosides in cerebral cortex, hippocampus and cerebellum was respectively acquired by electrospray ionization (ESI) MS and MALDI MSI, and the data were compared for reliability evaluation of MALDI MSI. Further, applying MALDI MSI technology, 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). PMID:27142336

  15. The total synthesis of a ganglioside Hp-s1 analogue possessing neuritogenic activity by chemoselective activation glycosylation.

    PubMed

    Tsai, Yow-Fu; Shih, Cheng-Hua; Su, Yu-Ting; Yao, Chun-Hsu; Lian, Jang-Feng; Liao, Chun-Chen; Hsia, Ching-Wu; Shui, Hao-Ai; Rani, Rashmi

    2012-02-07

    The total synthesis of ganglioside 2, an analogue of the ganglioside Hp-s1 (1) which displays neuritogenic activity toward the rat pheochromocytoma cell line PC-12 cell in the presence of nerve growth factor (NGF) with an effect (34.0%) greater than that of the mammalian ganglioside GM 1 (25.4%), was accomplished by applying a chemoselective-activation glycosylation strategy. Moreover, we also demonstrate that the synthesized ganglioside 2 exhibited neuritogenic activity toward the human neuroblastoma cell line SH-SY5Y without the presence of NGF.

  16. (1)H relaxivity of water in aqueous suspensions of Gd(3+)-loaded NaY nanozeolites and AlTUD-1 mesoporous material: the influence of Si/Al ratio and pore size.

    PubMed

    Norek, Małgorzata; Neves, Isabel C; Peters, Joop A

    2007-07-23

    The results of a (1)H nuclear magnetic relaxation dispersion (NMRD) and EPR study on aqueous suspensions of Gd(3+)-loaded NaY nanozeolites and AlTUD-1 mesoporous material are described. Upon increase of the Si/Al ratio from 1.7 to 4.0 in the Gd(3+)-loaded zeolites, the relaxation rate per mM Gd(3+) (r1) at 40 MHz and 25 degrees C increases from 14 to 27 s(-)1 mM(-1). The NMRD and EPR data were fitted with a previously developed two-step model that considers the system as a concentrated aqueous solution of Gd(3+) in the interior of the zeolite that is in exchange with the bulk water outside the zeolite. The results show that the observed increase in relaxivity can mainly be attributed to the residence lifetime of the water protons in the interior of the material, which decreased from 0.3 to 0.2 micros, upon the increase of the Si/Al ratio. This can be explained by the decreased interaction of water with the zeolite walls as a result of the increased hydrophobicity. The importance of the exchange rate of water between the inside and the outside of the material was further demonstrated by the relatively high relaxivity (33 s(-1) mM(-1) at 40 MHz, 25 degrees C) observed for a suspension of the Gd(3+)-loaded mesoporous material AlTUD-1. Unfortunately, Gd(3+) leaches rather easily from that material, but not from the Gd(3+)-loaded NaY zeolites, which may have potential as contrast agents for magnetic resonance imaging.

  17. Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside biosynthesis.

    PubMed

    Harlalka, Gaurav V; Lehman, Anna; Chioza, Barry; Baple, Emma L; Maroofian, Reza; Cross, Harold; Sreekantan-Nair, Ajith; Priestman, David A; Al-Turki, Saeed; McEntagart, Meriel E; Proukakis, Christos; Royle, Louise; Kozak, Radoslaw P; Bastaki, Laila; Patton, Michael; Wagner, Karin; Coblentz, Roselyn; Price, Joy; Mezei, Michelle; Schlade-Bartusiak, Kamilla; Platt, Frances M; Hurles, Matthew E; Crosby, Andrew H

    2013-12-01

    Glycosphingolipids are ubiquitous constituents of eukaryotic plasma membranes, and their sialylated derivatives, gangliosides, are the major class of glycoconjugates expressed by neurons. Deficiencies in their catabolic pathways give rise to a large and well-studied group of inherited disorders, the lysosomal storage diseases. Although many glycosphingolipid catabolic defects have been defined, only one proven inherited disease arising from a defect in ganglioside biosynthesis is known. This disease, because of defects in the first step of ganglioside biosynthesis (GM3 synthase), results in a severe epileptic disorder found at high frequency amongst the Old Order Amish. Here we investigated an unusual neurodegenerative phenotype, most commonly classified as a complex form of hereditary spastic paraplegia, present in families from Kuwait, Italy and the Old Order Amish. Our genetic studies identified mutations in B4GALNT1 (GM2 synthase), encoding the enzyme that catalyzes the second step in complex ganglioside biosynthesis, as the cause of this neurodegenerative phenotype. Biochemical profiling of glycosphingolipid biosynthesis confirmed a lack of GM2 in affected subjects in association with a predictable increase in levels of its precursor, GM3, a finding that will greatly facilitate diagnosis of this condition. With the description of two neurological human diseases involving defects in two sequentially acting enzymes in ganglioside biosynthesis, there is the real possibility that a previously unidentified family of ganglioside deficiency diseases exist. The study of patients and animal models of these disorders will pave the way for a greater understanding of the role gangliosides play in neuronal structure and function and provide insights into the development of effective treatment therapies.

  18. Brain gangliosides: functional ligands for myelin stability and the control of nerve regeneration.

    PubMed

    Vyas, A A; Schnaar, R L

    2001-07-01

    Gangliosides, sialylated glycosphingolipids which are the predominant glycans on vertebrate nerve cell surfaces, are emerging as components of membrane rafts, where they can mediate important physiological functions. Myelin associated glycoprotein (MAG), a minor constituent of myelin, is a sialic acid binding lectin with two established physiological functions: it is involved in myelin-axon stability and cytoarchitecture, and controls nerve regeneration. MAG is found selectively on the myelin membranes directly apposed to the axon surface, where it has been proposed to mediate myelin-axon interactions. Although the nerve cell surface ligands for MAG remain to be established, evidence supports a functional role for sialylated glycoconjugates. Here we review recent studies that reflect on the role of gangliosides, sialylated glycosphingolipids, as functional MAG ligands. MAG binds to gangliosides with the terminal sequence 'NeuAc alpha 3Gal beta 3GalNAc' which is found on the major nerve gangliosides GD1a and GT1b. Gangliosides lacking that terminus (e.g., GM1 or GD1b), or having any biochemical modification of the terminal NeuAc residue fail to support MAG binding. Genetically engineered mice lacking the GalNAc transferase required for biosynthesis of the 'NeuAc alpha 3Gal beta 3GalNAc' terminus have grossly impaired myelination and progressive neurodegeneration. Notably the MAG level in these animals is dysregulated. Furthermore, removal of NeuAc residues from nerve cells reverses MAG-mediated inhibition of neuritogenesis, and neurons from mice lacking the 'NeuAc alpha 3 Gal beta 3GalNAc' terminus have an attenuated response to MAG. Cross-linking nerve cell surface gangliosides can mimic MAG-mediated inhibition of nerve regeneration. Taken together these observations implicate gangliosides as functional MAG ligands.

  19. Distribution of mono-, di- and trisialo gangliosides in the brain of Actinopterygian fishes.

    PubMed

    Viljetić, Barbara; Labak, Irena; Majić, Senka; Stambuk, Anamaria; Heffer, Marija

    2012-09-01

    Mono-, di- and trisialo gangliosides are major glycosphingolipids in the brain of higher vertebrates involved in lipid raft assembly. In contrast, the fish brain is abundant in polisialo-gangliosides, whose function is implicated in the modulation of repulsive and attractive intercellular interactions during embryonic development and a temperature adaptation process. The histological distribution of gangliosides is usually studied in rodent and mammalian brains, but to date it has not been described in the case of fish brain. Gangliosides were extracted from adult brains of trout, carp and zebrafish and separated by TLC. High-affinity anti-ganglioside (GM1, GD1a, GD1b, GT1b) IgG antibodies were used for immunohistochemistry. In trout and carp brains GM1 and GT1b are expressed in the same neuronal cell bodies from the telencephalon to the spinal cord. In zebrafish brain GM1 was not detected, whereas GT1b is a general neuropil staining. GD1a is specific for unmyelinated parallel fibers in carp and zebrafish brains as well as parallel fibers in the molecular layer of all cerebellar divisions. In trout brain GD1b is found in parallel fibers of the cerebellum, but not in the tectum mesencephali. GD1b is expressed in zebrafish neuronal cell bodies. Each studied species has a different expression of complex gangliosides. GT1b is widely present, whereas GD1a and GD1b appear in a specific group of unmyelinated fibers and could be used as their specific marker. This is the first report on mono-, di- and trisialo ganglioside (GM1, GD1a, GD1b and GT1b) distribution in the brain of adult Actinopterygian fishes. This article is part of a Special Issue entitled Glycoproteomics. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. The quantum cutting of Tb(3+) in Ca(6)Ln(2)Na(2)(PO(4))(6)F(2) (Ln = Gd, La) under VUV-UV excitation: with and without Gd(3+).

    PubMed

    Xie, Mubiao; Tao, Ye; Huang, Yan; Liang, Hongbin; Su, Qiang

    2010-12-20

    The VUV-vis spectroscopic properties of Tb(3+) activated fluoro-apatite phosphors Ca(6)Ln(2-x)Tb(x)Na(2)(PO(4))(6)F(2) (Ln = Gd, La) were studied. The results show that phosphors Ca(6)Gd(2-x)Tb(x)Na(2)(PO(4))(6)F(2) with Gd(3+) ions as sensitizers have intense absorption in the VUV range. The emission color of both phosphors can be tuned from blue to green by changing the doping concentration of Tb(3+) under 172 nm excitation. The visible quantum cutting (QC) via cross relaxation between Tb(3+) ions was observed in cases with and without Gd(3+). Though QC can be realized in phosphors Ca(6)La(2-x)Tb(x)Na(2)(PO(4))(6)F(2), we found that Gd(3+)-containg phosphors have a higher QC efficiency, confirming that the Gd(3+) ion indeed plays an important role during the quantum cutting process. In addition, the energy transfer process from Gd(3+) to Tb(3+) as well as (5)D(3)-(5)D(4) cross relaxation was investigated and discussed in terms of luminescence spectra and decay curves.

  1. Composition-property relationships in (Gd3-xLux)(GayAl5-y)O12:Ce (x = 0, 1, 2, 3 and y = 0, 1, 2, 3, 4) multicomponent garnet scintillators

    NASA Astrophysics Data System (ADS)

    Luo, Jialiang; Wu, Yuntao; Zhang, Guoqing; Zhang, Huaijin; Ren, Guohao

    2013-12-01

    The (LuxGd3-x)(GayAl5-y)O12:Ce (x = 0, 1, 2, 3 and y = 0, 1, 2, 3, 4) scintillating polycrystalline powders were prepared by high temperature solid state reaction method. A pure cubic phase was confirmed in all samples by X-ray diffraction (XRD). X-ray excited luminescence (XEL), photoluminescence excitation and emission spectra were employed to study the influence of Gd3+-Ga3+ admixture on the luminescent mechanism of Ce3+ as well as the energy transfer from Gd3+ to Ce3+. The band-gap structures with varying Gd3+ and Ga3+ content were constructed to understand the luminescence behaviors. In addition, thermoluminescence spectra (TL) were utilized to identify the moving of conduction band (CB) by monitoring the shift of the corresponding TL peaks. Finally, it was found that incorporation of 40 mol% (y = 2) Ga3+ and 33.3-66.7 mol% (x = 1-2) Gd3+ could secure enough energy-separation between CB and 5d1 of Ce3+ avoiding thermal ionization effect at utmost, and bury the antisite defect traps into CB, and in turn achieving the optimum scintillation efficiency.

  2. Synthesis and complexation properties of DTPA-N,N''-bis[bis(n-butyl)]-N'-methyl-tris(amide). Kinetic stability and water exchange of its Gd3+ complex.

    PubMed

    Jaszberényi, Z; Tóth, E; Kálai, T; Király, R; Burai, L; Brücher, E; Merbach, A E; Hideg, K

    2005-02-21

    A novel DTPA-tris(amide) derivative ligand, DTPA-N,N''-bis[bis(n-butyl)]-N'-methyl-tris(amide)(H2L3) was synthesized. With Gd3+, it forms a positively charged [Gd(L3)]+ complex, whereas with Cu2+ and Zn2+ [ML3], [MHL3]+ and [M2L3]2+ species are formed. The protonation constants of H2L3 and the stability constants of the complexes were determined by pH potentiometry. The stability constants are lower than those for DTPA-N,N''-bis[bis(n-butyl)amide)](H3L2), due to the lower negative charge and reduced basicity of the amine nitrogens in (L3)2-. The kinetic stability of [Gd(L3)]+ was characterised by the rates of metal exchange reactions with Eu3+, Cu2+ and Zn2+. The exchange reactions, which occur via proton and metal ion assisted dissociation of [Gd(L3)]+, are significantly slower than for [Gd(DTPA)]2-, since the amide groups cannot be protonated and interact only weakly with the attacking metal ions. The relaxivities of [Gd(L2)] and [Gd(L3)]+ are constant between 10-20 degrees C, indicating a relatively slow water exchange. Above 25 degrees C, the relaxivities decrease, similarly to other Gd3+ DTPA-bis(amide) complexes. The pH dependence of the relaxivities for [Gd(L3)]+ shows a minimum at pH approximately 9, thus differs from the behaviour of Gd3+-DTPA-bis(amides) which have constant relaxivities at pH 3-8 and an increase below and above. The water exchange rates for [Gd(L2)(H2O)] and [Gd(L3)(H2O)]+, determined from a variable temperature (17)O NMR study, are lower than that for [Gd(DTPA)(H2O)]2-. This is a consequence of the lower negative charge and decreased steric crowding at the water binding site in amides as compared to carboxylate analogues. Substitution of the third acetate of DTPA5- with an amide, however, results in a less pronounced decrease in kex than substitution of the first two acetates. The activation volumes derived from a variable pressure (17)O NMR study prove a dissociative interchange and a limiting dissociative mechanism for [Gd(L2)(H2O

  3. Fibrillar organization of fibronectin is expressed coordinately with cell surface gangliosides in a variant murine fibroblast

    PubMed Central

    1986-01-01

    NCTC 2071A cells, a line of transformed murine fibroblasts, grow in serum-free medium, are deficient in gangliosides, synthesize fibronectin, but do not retain and organize it on the cell surface. When the cells are exposed to exogenous gangliosides, fibrillar strands of fibronectin become attached to the cell surface. A morphologically distinct variant of NCTC 2071A cells was observed to both retain cell surface fibronectin and organize it into a fibrillar network when the cells were stained with anti-fibronectin antibodies and a fluorescent second antibody. A revertant cell type appeared to resemble the parental NCTC 2071A cells in terms of morphology and fibronectin organization. All three cell types were subjected to mild NaIO4 oxidation and reduction with KB3H4 of very high specific radioactivity in order to label the sialic acid residues of surface gangliosides. The variant had much more surface gangliosides than the parental, particularly more complex gangliosides corresponding to GM1 and GD1a. The surface gangliosides of the revertant were intermediate between the parental and the variant. By using sialidase, which hydrolyzes GD1a to GM1, and 125I-labeled cholera toxin, which binds specifically to GM1, the identity and levels of these gangliosides were confirmed in the three cell types. When variant cells were exposed to sialidase for 2 d, there appeared to be little change in fibronectin organization. Concomitant treatment of the cells with the B subunit of cholera toxin, which bound to all the surface GM1 including that generated by the sialidase, however, eliminated the fibrillar network of fibronectin. In addition, exposure of the variant cells to a 70,000-mol-wt fragment of fibronectin, which lacks the cell attachment domain but contains a matrix assembly domain, inhibited the formation of fibers. Finally, all three cell types were assayed for their ability to attach to and spread on fibronectin-coated surfaces; no significant differences were found

  4. Synaptotagmin II and gangliosides bind independently with botulinum neurotoxin B but each restrains the other.

    PubMed

    Atassi, M Zouhair; Taruishi, Midori; Naqvi, Masooma; Steward, Lance E; Aoki, K Roger

    2014-06-01

    Botulinum neurotoxin type B (BoNT/B) initiates its toxicity by binding to synaptotagmin II (SytII) and gangliosides GD1a and GT1b on the neural membrane. We synthesized two 27-residue peptides that carry the BoNT/B binding sites on mouse SytII (mSytII 37-63) or human SytII (hSytII 34-60). BoNT/B bound to these peptides, but showed substantially higher binding to mSytII peptide than to hSytII peptide. The mSytII peptide inhibited almost completely BoNT/B binding to synaptosomes (snps) and displayed a high affinity. BoNT/B bound strongly to mSytII peptide and binding was inhibited by the peptide. Binding of BoNT/B to snps was also inhibited (~80 %) by a larger excess of gangliosides GD1a or GT1b. The mSytII peptide inhibited very strongly (at least 80 %) the toxin binding to snps, while the two gangliosides were much less efficient inhibitors requiring much larger excess to achieve similar inhibition levels. Furthermore, gangliosides GD1a or GT1b inhibited BoNT/B binding to mSytII peptide at a much larger excess than the inhibition by mSytII peptide. Conversely, BoNT/B bound well to each ganglioside and binding could be inhibited by the correlate ganglioside and much less efficiently by the mSytII peptide. There was no apparent collaboration between mSytII peptide and either ganglioside. mSytII peptide displayed some protective activity in vivo in mice against a lethal BoNT/B dose. We concluded that SytII peptide and gangliosides bind independently but, with their binding sites on BoNT/B being spatially close, each can influence BoNT/B binding to the other due to regional conformational perturbations or steric interference or both. Ganglioside involvement in BoNT/B binding might help in toxin translocation and endocytosis.

  5. Trap depth and color variation of Ce3+-Cr3+ co-doped Gd3(Al,Ga)5O12 garnet persistent phosphors

    NASA Astrophysics Data System (ADS)

    Asami, Kazuki; Ueda, Jumpei; Tanabe, Setsuhisa

    2016-12-01

    Persistent luminescent properties in Ce3+-Cr3+ codoped Gd3Al5-xGaxO12 garnet (GAGG:Ce-Cr) solid solution have been investigated. The persistent luminescent color is shifted from orange to yellowish green with increasing Ga content because Ce3+: 5d level splitting becomes much weaker. The depth of electron trap introduced by Cr codoping was estimated from the intense thermoluminescence glow peak by the initial rise method. The trap depth decreases from 0.56 eV to 0.29 eV with increasing Ga content. The shift can be explained by downshift of bottom of conduction band. From the persistent luminescence decay curve measurement after ceasing 450 nm blue illumination, the samples with x = 2.5 exhibited the longest persistent luminescence for 405 min until the luminance becomes 2 mcd/m2 in GAGG:Ce-Cr phosphors.

  6. High-efficiency Watt-level picosecond pulse generation based on Yb:Gd3AlxGa5-xO12 crystal

    NASA Astrophysics Data System (ADS)

    Li, Yanbin; Jia, Zhitai; Lou, Fei; Zhang, Baitao; He, Jingliang; Tao, Xutang

    2015-07-01

    A diode-pumped passively mode-locked Yb3+:Gd3Al0.5Ga4.5O12 (Yb:GAGG) laser has been investigated by using a semiconductor saturable absorber mirror (SESAM) for the first time. Pulses with duration of 1.6 ps were produced at the central wavelength of 1027.8 nm. At the absorbed pump power of 8.4 W, the maximum average output power of 1.02 W was obtained with the repetition rate of 45 MHz. The corresponding single pulse energy and the peak power were calculated to be 22.7 nJ and 14.2 kW, respectively.

  7. High-efficiency femtosecond Yb:Gd3Al(0.5)Ga(4.5)O12 mode-locked laser based on reduced graphene oxide.

    PubMed

    Lou, Fei; Cui, Liang; Li, Yan-Bin; Hou, Jia; He, Jing-Liang; Jia, Zhi-Tai; Liu, Jing-Quan; Zhang, Bai-Tao; Yang, Ke-Jian; Wang, Zhao-Wei; Tao, Xu-Tang

    2013-10-15

    A diode-pumped Yb-doped Gd(3)Al(0.5)Ga(4.5)O(12) mode-locked bulk laser based on chemically reduced graphene oxide (RGO) has been demonstrated for the first time to our best knowledge. Pulses with duration of 643 fs were produced at the central wavelength of 1041.1 nm. A maximum average output power of 0.8 W was obtained from the RGO mode-locked laser, corresponding to a slope efficiency of 20.1% and a peak power of 27.6 kW. The results indicate that RGO is suitable for obtaining high-power and high-efficiency ultrafast lasers.

  8. Anisotropic phase diagram and spin fluctuations of the hyperkagome magnet Gd3Ga5O12 as revealed by sound velocity measurements

    NASA Astrophysics Data System (ADS)

    Rousseau, Alexandre; Parent, Jean-Michel; Quilliam, Jeffrey A.

    2017-08-01

    Sound velocity and attenuation measurements on the frustrated garnet material Gd3Ga5O12 (GGG) are presented as a function of field and temperature, with two different magnetic field orientations: [100 ] and [110 ] . We demonstrate that the phase diagram is highly anisotropic, with two distinct field-induced ordered phases for H ||[110 ] and only one for H ||[100 ] . Extensive lattice softening is found to occur at low fields, which can be associated with spin fluctuations. However, deep within the spin liquid phase a low-temperature stiffening of the lattice and reduced attenuation provide evidence for a spin gap which may be related to short-range antiferromagnetic correlations over minimal ten-spin loops.

  9. Raft-based interactions of gangliosides with a GPI-anchored receptor.

    PubMed

    Komura, Naoko; Suzuki, Kenichi G N; Ando, Hiromune; Konishi, Miku; Koikeda, Machi; Imamura, Akihiro; Chadda, Rahul; Fujiwara, Takahiro K; Tsuboi, Hisae; Sheng, Ren; Cho, Wonhwa; Furukawa, Koichi; Furukawa, Keiko; Yamauchi, Yoshio; Ishida, Hideharu; Kusumi, Akihiro; Kiso, Makoto

    2016-06-01

    Gangliosides, glycosphingolipids containing one or more sialic acid(s) in the glyco-chain, are involved in various important physiological and pathological processes in the plasma membrane. However, their exact functions are poorly understood, primarily because of the scarcity of suitable fluorescent ganglioside analogs. Here, we developed methods for systematically synthesizing analogs that behave like their native counterparts in regard to partitioning into raft-related membrane domains or preparations. Single-fluorescent-molecule imaging in the live-cell plasma membrane revealed the clear but transient colocalization and codiffusion of fluorescent ganglioside analogs with a fluorescently labeled glycosylphosphatidylinisotol (GPI)-anchored protein, human CD59, with lifetimes of 12 ms for CD59 monomers, 40 ms for CD59's transient homodimer rafts in quiescent cells, and 48 ms for engaged-CD59-cluster rafts, in cholesterol- and GPI-anchoring-dependent manners. The ganglioside molecules were always mobile in quiescent cells. These results show that gangliosides continually and dynamically exchange between raft domains and the bulk domain, indicating that raft domains are dynamic entities.

  10. Oligosaccharide-specific receptors for gangliosides in the central nervous system

    SciTech Connect

    Tiemeyer, M.J.

    1989-01-01

    Synthetic ganglioside-derivatized proteins were prepared, radiolabeled, and used as ligands to search for specific receptors on rat brain membranes. Chemical derivatization schemes were designed to covalently link gangliosides (specifically, G{sub T1b}) to bovine serum albumin (BSA) via their ceramide portions leaving the glycolipid oligosaccharides intact and limiting the ability of the ganglioside moiety to interact with brain membranes non-specifically by insertion or hydrophobic adsorption. Following characterization and tyrosine-radioiodination, {sup 125}I-(G{sub T1b}){sub 4} BSA (BSA derivatized with 4 G{sub T1b} moieties/protein molecule), revealed a high affinity and saturable binding site on rat brain membranes. Pretreatment of brain membranes with low concentrations of trypsin blocked binding, consistent with the presence of a proteinaceous ganglioside-receptor. The most potent lipid inhibitors of {sup 125}I-(G{sub T1b}){sub 4}BSA binding were the gangliosides G{sub T1b}, G{sub D1b}, and G{sub Q1b} which share common structural features in their oligosaccharide portions; maximal inhibitory potency required a full length gangliotetraose oligosaccharide core and {alpha}2-8 linked sialic acid.

  11. Localization and imaging of gangliosides in mouse brain tissue sections by laserspray ionization inlet[S

    PubMed Central

    Richards, Alicia L.; Lietz, Christopher B.; Wager-Miller, James; Mackie, Ken; Trimpin, Sarah

    2012-01-01

    A new ionization method for the analysis of fragile gangliosides without undesired fragmentation or salt adduction is presented. In laserspray ionization inlet (LSII), the matrix/analyte sample is ablated at atmospheric pressure, and ionization takes place in the ion transfer capillary of the mass spectrometer inlet by a process that is independent of a laser wavelength or voltage. The softness of LSII allows the identification of gangliosides up to GQ1 with negligible sialic acid loss. This is of importance to the field of MS imaging, as undesired fragmentation has made it difficult to accurately map the spatial distribution of fragile ganglioside lipids in tissue. Proof-of-principle structural characterization of endogenous gangliosides using MSn fragmentation of multiply charged negative ions on a LTQ Velos and subsequent imaging of the GD1 ganglioside is demonstrated. This is the first report of multiply charged negative ions using inlet ionization. We find that GD1 is detected at higher levels in the mouse cortex and hippocampus compared with the thalamus. In LSII with the laser aligned in transmission geometry relative to the inlet, images were obtained in approximately 60 min using an inexpensive nitrogen laser. PMID:22262808

  12. Bovine lactoferrin decreases cholera-toxin-induced intestinal fluid accumulation in mice by ganglioside interaction.

    PubMed

    Rivera, Fulton P; Medina, Anicia M; Bezada, Sandra; Valencia, Roberto; Bernal, María; Meza, Rina; Maves, Ryan C; Ochoa, Theresa J

    2013-01-01

    Secretory diarrhea caused by cholera toxin (CT) is initiated by binding of CT's B subunit (CTB) to GM1-ganglioside on the surface of intestinal cells. Lactoferrin, a breast milk glycoprotein, has shown protective effect against several enteropathogens. The aims of this study were to determine the effect of bovine-lactoferrin (bLF) on CT-induced intestinal fluid accumulation in mice, and the interaction between bLF and CT/CTB with the GM1-ganglioside receptor. Fluid accumulation induced by CT was evaluated in the mouse ileal loop model using 56 BALB/c mice, with and without bLF added before, after or at the same time of CT administration. The effect of bLF in the interaction of CT and CTB with GM1-ganglioside was evaluated by a GM1-enzyme-linked immunosorbent assay. bLF decreased CT-induced fluid accumulation in the ileal loop of mice. The greatest effect was when bLF was added before CT (median, 0.066 vs. 0.166 g/cm, with and without bLF respectively, p<0.01). We conclude that bLF decreases binding of CT and CTB to GM1-ganglioside, suggesting that bLF suppresses CT-induced fluid accumulation by blocking the binding of CTB to GM1-ganglioside. bLF may be effective as adjunctive therapy for treatment of cholera diarrhea.

  13. Partial synthesis of ganglioside and lysoganglioside lipoforms as internal standards for MS quantification.

    PubMed

    Gantner, Martin; Schwarzmann, Günter; Sandhoff, Konrad; Kolter, Thomas

    2014-12-01

    Within recent years, ganglioside patterns have been increasingly analyzed by MS. However, internal standards for calibration are only available for gangliosides GM1, GM2, and GM3. For this reason, we prepared homologous internal standards bearing nonnatural fatty acids of the major mammalian brain gangliosides GM1, GD1a, GD1b, GT1b, and GQ1b, and of the tumor-associated gangliosides GM2 and GD2. The fatty acid moieties were incorporated after selective chemical or enzymatic deacylation of bovine brain gangliosides. For modification of the sphingoid bases, we developed a new synthetic method based on olefin cross metathesis. This method was used for the preparation of a lyso-GM1 and a lyso-GM2 standard. The total yield of this method was 8.7% for the synthesis of d17:1-lyso-GM1 from d20:1/18:0-GM1 in four steps. The title compounds are currently used as calibration substances for MS quantification and are also suitable for functional studies. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

  14. Renal cell carcinoma–derived gangliosides suppress nuclear factor-κB activation in T cells

    PubMed Central

    Uzzo, Robert G.; Rayman, Patricia; Kolenko, Vladimir; Clark, Peter E.; Cathcart, Martha K.; Bloom, Tracy; Novick, Andrew C.; Bukowski, Ronald M.; Hamilton, Thomas; Finke, James H.

    1999-01-01

    Activation of the transcription factor nuclear factor-κB (NFκB) is impaired in T cells from patients with renal cell carcinomas (RCCs). In circulating T cells from a subset of patients with RCCs, the suppression of NFκB binding activity is downstream from the stimulus-induced degradation of the cytoplasmic factor IκBα. Tumor-derived soluble products from cultured RCC explants inhibit NFκB activity in T cells from healthy volunteers, despite a normal level of stimulus-induced IκBα degradation in these cells. The inhibitory agent has several features characteristic of a ganglioside, including sensitivity to neuraminidase but not protease treatment; hydrophobicity; and molecular weight less than 3 kDa. Indeed, we detected gangliosides in supernatants from RCC explants and not from adjacent normal kidney tissue. Gangliosides prepared from RCC supernatants, as well as the purified bovine gangliosides Gm1 and Gd1a, suppressed NFκB binding activity in T cells and reduced expression of the cytokines IL-2 and IFN-γ. Taken together, our findings suggest that tumor-derived gangliosides may blunt antitumor immune responses in patients with RCCs. PMID:10491412

  15. Bovine Lactoferrin Decreases Cholera-Toxin-Induced Intestinal Fluid Accumulation in Mice by Ganglioside Interaction

    PubMed Central

    Rivera, Fulton P.; Medina, Anicia M.; Bezada, Sandra; Valencia, Roberto; Bernal, María; Meza, Rina; Maves, Ryan C.; Ochoa, Theresa J.

    2013-01-01

    Secretory diarrhea caused by cholera toxin (CT) is initiated by binding of CT’s B subunit (CTB) to GM1-ganglioside on the surface of intestinal cells. Lactoferrin, a breast milk glycoprotein, has shown protective effect against several enteropathogens. The aims of this study were to determine the effect of bovine-lactoferrin (bLF) on CT-induced intestinal fluid accumulation in mice, and the interaction between bLF and CT/CTB with the GM1-ganglioside receptor. Fluid accumulation induced by CT was evaluated in the mouse ileal loop model using 56 BALB/c mice, with and without bLF added before, after or at the same time of CT administration. The effect of bLF in the interaction of CT and CTB with GM1-ganglioside was evaluated by a GM1-enzyme-linked immunosorbent assay. bLF decreased CT-induced fluid accumulation in the ileal loop of mice. The greatest effect was when bLF was added before CT (median, 0.066 vs. 0.166 g/cm, with and without bLF respectively, p<0.01). We conclude that bLF decreases binding of CT and CTB to GM1-ganglioside, suggesting that bLF suppresses CT-induced fluid accumulation by blocking the binding of CTB to GM1-ganglioside. bLF may be effective as adjunctive therapy for treatment of cholera diarrhea. PMID:23580005

  16. Detection of Sendai virus receptor, the ganglioside GDla, in target tissue (mouse lung)

    SciTech Connect

    Markwell, M.A.K.; Sato, E.

    1986-05-01

    Previously the authors had shown that the gangliosides GDla, GTlb, and GQlb derived from brain function as receptors for the paramyxovirus Sendai virus by their ability to induce infection when incubated with receptor-deficient cells. Analyses of MDBK, HeLa, and MDCK cells in culture demonstrated that these putative receptors were present in host cells in the quantities required for infection. The primary site of infection for Sendai virus in the whole animal is the respiratory tract, culminating in the lung. Therefore, the ganglioside content of this target organ was analyzed to determine the endogenous receptor population available to Sendai virus. The total ganglioside fraction of lung was resolved into individual species by HPTLC. Gangliosides of the gangliotetraose series were identified by the specific binding of /sup 125/I-labeled tetanus and cholera toxins before and after exposure with sialidase. In this manner one of the major resorcinol-positive bands was identified as GDla. Evidence of the more complex ganglioside receptors for Sendai virus was also seen.

  17. Partial synthesis of ganglioside and lysoganglioside lipoforms as internal standards for MS quantification

    PubMed Central

    Gantner, Martin; Schwarzmann, Günter; Sandhoff, Konrad; Kolter, Thomas

    2014-01-01

    Within recent years, ganglioside patterns have been increasingly analyzed by MS. However, internal standards for calibration are only available for gangliosides GM1, GM2, and GM3. For this reason, we prepared homologous internal standards bearing nonnatural fatty acids of the major mammalian brain gangliosides GM1, GD1a, GD1b, GT1b, and GQ1b, and of the tumor-associated gangliosides GM2 and GD2. The fatty acid moieties were incorporated after selective chemical or enzymatic deacylation of bovine brain gangliosides. For modification of the sphingoid bases, we developed a new synthetic method based on olefin cross metathesis. This method was used for the preparation of a lyso-GM1 and a lyso-GM2 standard. The total yield of this method was 8.7% for the synthesis of d17:1-lyso-GM1 from d20:1/18:0-GM1 in four steps. The title compounds are currently used as calibration substances for MS quantification and are also suitable for functional studies. PMID:25341943

  18. Influence of tunicamycin, sialidase, and cholera toxin on gangliosides and T-lymphocyte responses to interleukin 2

    SciTech Connect

    Semmes, O.J.; Bailey, J.M.; Merritt, W.D.

    1986-05-01

    The authors have shown that gangliosides inhibit interleukin 2 (IL 2)-dependent proliferation of murine T cells. Tunicamycin (TM), sialidase, and cholera toxin-..beta.. subunit (..beta..-CT) are known modulators of cell surface glycoconjugates. To test the possible role of endogenous gangliosides in T cell responses to IL-2, the effect of these agents on ganglioside expression and cell proliferation was studied. Gangliosides were labelled for 24 hrs with /sup 3/H-glucosamine/galactose in the presence of IL-2 and purified sialidase, TM or ..beta..-CT. Gangliosides were isolated and the species separated by TLC. Alternatively, proliferation was assayed by /sup 3/H-thymidine uptake after 48 hrs culture. TM treatment at a concentration (10 ..mu..g/ml) that completely inhibited proliferation resulted in a 86% reduction of incorporation of saccharide precursors into gangliosides compared to a 50% reduction into proteins. Sialidase treatment (0.1 IU/ml) resulted in a 70% inhibition of proliferation and 30% reduction of radiolabel into gangliosides, of which 3 species were specifically reduced. ..beta..-CT, which binds to GM/sub 1/ and to a lesser extent GD/sub 1a/, caused a 50% reduction in proliferation response at 35 units/ml. The results support the hypothesis that gangliosides are involved in IL-2-dependent proliferation.

  19. Synthesis and luminescent properties of Eu3+, Eu3+/Bi3+ and Gd3+ codoped YAG:Ce3+ phosphors and their potential applications in warm white light-emitting diodes

    NASA Astrophysics Data System (ADS)

    Yang, Yuguo; Li, Jing; Liu, Bing; Zhang, Yuanyuan; Lv, Xianshun; Wei, Lei; Wang, Xuping; Xu, Jianhua; Yu, Huajian; Hu, Yanyan; Zhang, Huadi; Ma, Ling; Wang, Jiyang

    2017-10-01

    A series of YAG:Ce3+/Eu3+, YAG:Ce3+/Eu3+/Bi3+ and YAG:Ce3+/Gd3+ phosphors were synthesized by a co-precipitation method. The results suggest that all of phosphors have the cubic phase and nearly spherical morphology. However, the red emission can be produced by codoping Eu3+ and Eu3+/Bi3+ ions in YAG:Ce3+, and the codoped Gd3+ ions can induce the red-shift of Ce3+ emission. These results suggest that the Eu3+, Eu3+/Bi3+ and Gd3+ ions can be used to decrease the correlated color temperature and increase the color-rendering index of white light-emitting diodes based on InGaN blue chip and YAG:Ce3+ phosphors.

  20. Isolation and characterization of a novel phytosphingosine-containing GM2 ganglioside from mullet roe (Mugil cephalus).

    PubMed

    Li, Y T; Hirabayashi, Y; DeGasperi, R; Yu, R K; Ariga, T; Koerner, T A; Li, S C

    1984-07-25

    The major ganglioside from the roe of striped mullet (Mugil cephalus) has been isolated and purified. Compositional analysis of this ganglioside revealed that it contained an equimolar ratio of the following residues: N-acetylneuraminic acid, N-acetylgalactosamine, galactose, glucose, and the long-chain base. Further structural studies by sequential enzymatic hydrolysis, permethylation analysis, and proton NMR spectroscopy indicated that the structure of the oligosaccharide moiety was identical to that of GM2 ganglioside from human brain: GalNAc beta 1----4Gal beta 1----4(3----2 alpha NeuAc)-Glc----ceramide. This ganglioside, however, differed from brain GM2 in its ceramide portion. The most striking differences are the presence of large amounts of C18 and C20 phytosphingosine (over 80% of the total long-chain bases) and the preponderance of monounsaturated alpha-hydroxy fatty acids (over 80%). Such a phytosphingosine-containing GM2 ganglioside has never been reported.

  1. Effect of simulated gastrointestinal digestion on sialic acid and gangliosides present in human milk and infant formulas.

    PubMed

    Lacomba, Ramón; Salcedo, Jaime; Alegría, Amparo; Barberá, Reyes; Hueso, Pablo; Matencio, Esther; Lagarda, M Jesús

    2011-05-25

    The effects of simulated gastrointestinal digestion upon sialic acid and gangliosides in infant and follow-on formulas and human milk, as well as their bioaccessibility, have been evaluated. The gastric stage is the step that causes a greater decrease in sialic acid and ganglioside contents. The intestinal stage only decreases the total and individual contents of gangliosides. After gastrointestinal digestion, neither sialic acid nor gangliosides were found in the nonbioaccessible fraction. The highest bioaccessibility (100 × content in soluble fraction after gastrointestinal digestion/total content) of sialic acid is found in human milk (87%), followed by infant formula (77%) and follow-on formula (16%). In the case of gangliosides, the highest bioaccessibility is present in the follow-on formula (51%), followed by human milk (29%) and infant formula (5%).

  2. Apprehending ganglioside diversity: a comprehensive methodological approach[S

    PubMed Central

    Masson, Elodie A. Y.; Sibille, Estelle; Martine, Lucy; Chaux-Picquet, Fanny; Bretillon, Lionel; Berdeaux, Olivier

    2015-01-01

    Gangliosides (GGs) make a wide family of glycosphingolipids ubiquitously expressed in mammalian tissues and particularly abundant in the brain and nervous system. They exhibit a huge diversity due to structural variations in both their oligosaccharidic chain and ceramide moiety, which represent a real analytical challenge. Since their discovery in the 1940s, methods have persistently improved until the emergence of LC/MS, which offers a high level of specificity and sensitivity and is suitable with high-throughput profiling studies. We describe here a comprehensive approach relying on various techniques and aiming at fully characterizing GGs in biological samples. First, total GG content was determined by a biochemical assay. Second, GG class composition was assessed by high-performance thin-layer chromatography followed by colorimetric revelation. Then, ceramide types of GG classes were identified, and their relative quantification was performed thanks to the development of a powerful and reliable LC/MS method. Finally, ceramides were structurally characterized, and minor and less common GG classes were identified using high-resolution MS. These methods were applied to the rat retina to provide an exhaustive description of its GG composition, giving the base for a better understanding of the precise roles of GGs in this tissue. PMID:26142958

  3. Detection of N-glycolyated gangliosides in non-small-cell lung cancer using GMR8 monoclonal antibody.

    PubMed

    Hayashi, Nobuyoshi; Chiba, Hirofumi; Kuronuma, Koji; Go, Shinji; Hasegawa, Yoshihiro; Takahashi, Motoko; Gasa, Shinsei; Watanabe, Atsushi; Hasegawa, Tadashi; Kuroki, Yoshio; Inokuchi, Jinichi; Takahashi, Hiroki

    2013-01-01

    Gangliosides are glycosphingolipids found on the cell surface. They act as recognition molecules or signal modulators and regulate cell proliferation and differentiation. N-glycolylneuraminic acid (NeuGc)-containing gangliosides have been detected in some neoplasms in humans, although they are usually absent in normal human tissues. Our aim was to evaluate the presence of NeuGc-containing gangliosides including GM3 (NeuGc) and assess their relationship with the prognosis of non-small-cell lung cancer (NSCLC). NeuGc-containing ganglioside expression in NSCLC tissues was analyzed immunohistochemically using the mouse monoclonal antibody GMR8, which is specific for gangliosides with NeuGc alpha 2,3Gal-terminal structures. On the basis of NeuGc-containing ganglioside expression, we performed survival analysis. We also investigated the differences in the effects of GM3 (N-acetylneuraminic acid [NeuAc]) and GM3 (NeuGc) on inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase in A431 cells. As a result, the presence of NeuGc-containing gangliosides was evident in 86 of 93 (93.5%) NSCLC samples. The NSCLC patients with high NeuGc-containing ganglioside expression had a low overall survival rate and a significantly low progression-free survival rate. In the in vitro study, the inhibitory effect of GM3 on EGFR tyrosine kinase in A431 cells after exposure to GM3 (NeuGc) was lower than that after exposure to GM3 (NeuAc). In conclusion, NeuGc-containing gangliosides including GM3 (NeuGc) are widely expressed in NSCLC, and NeuGc-containing ganglioside expression is associated with patient survival. The difference in the effects of GM3 (NeuGc) and GM3 (NeuAc) on the inhibition of EGFR tyrosine kinase might contribute to improvement in the prognosis of NSCLC patients. © 2012 Japanese Cancer Association.

  4. Cross-Linking Mast Cell Specific Gangliosides Stimulates the Release of Newly Formed Lipid Mediators and Newly Synthesized Cytokines.

    PubMed

    Filho, Edismauro Garcia Freitas; da Silva, Elaine Zayas Marcelino; Zanotto, Camila Ziliotto; Oliver, Constance; Jamur, Maria Célia

    2016-01-01

    Mast cells are immunoregulatory cells that participate in inflammatory processes. Cross-linking mast cell specific GD1b derived gangliosides by mAbAA4 results in partial activation of mast cells without the release of preformed mediators. The present study examines the release of newly formed and newly synthesized mediators following ganglioside cross-linking. Cross-linking the gangliosides with mAbAA4 released the newly formed lipid mediators, prostaglandins D2 and E2, without release of leukotrienes B4 and C4. The effect of cross-linking these gangliosides on the activation of enzymes in the arachidonate cascade was then investigated. Ganglioside cross-linking resulted in phosphorylation of cytosolic phospholipase A2 and increased expression of cyclooxygenase-2. Translocation of 5-lipoxygenase from the cytosol to the nucleus was not induced by ganglioside cross-linking. Cross-linking of GD1b derived gangliosides also resulted in the release of the newly synthesized mediators, interleukin-4, interleukin-6, and TNF-α. The effect of cross-linking the gangliosides on the MAP kinase pathway was then investigated. Cross-linking the gangliosides induced the phosphorylation of ERK1/2, JNK1/2, and p38 as well as activating both NFκB and NFAT in a Syk-dependent manner. Therefore, cross-linking the mast cell specific GD1b derived gangliosides results in the activation of signaling pathways that culminate with the release of newly formed and newly synthesized mediators.

  5. Specific synthesis of neurostatin and gangliosides O-acetylated in the outer sialic acids using a sialate transferase.

    PubMed

    Romero-Ramírez, Lorenzo; García-Álvarez, Isabel; Campos-Olivas, Ramón; Gilbert, Michel; Goneau, Marie-France; Fernández-Mayoralas, Alfonso; Nieto-Sampedro, Manuel

    2012-01-01

    Gangliosides are sialic acid containing glycosphingolipids, commonly found on the outer leaflet of the plasma membrane. O-acetylation of sialic acid hydroxyl groups is one of the most common modifications in gangliosides. Studies on the biological activity of O-acetylated gangliosides have been limited by their scarcity in nature. This comparatively small change in ganglioside structure causes major changes in their physiological properties. When the ganglioside GD1b was O-acetylated in the outer sialic acid, it became the potent inhibitor of astroblast and astrocytoma proliferation called Neurostatin. Although various chemical and enzymatic methods to O-acetylate commercial gangliosides have been described, O-acetylation was nonspecific and produced many side-products that reduced the yield. An enzyme with O-acetyltransferase activity (SOAT) has been previously cloned from the bacteria Campylobacter jejuni. This enzyme catalyzed the acetylation of oligosaccharide-bound sialic acid, with high specificity for terminal alpha-2,8-linked residues. Using this enzyme and commercial gangliosides as starting material, we have specifically O-acetylated the gangliosides' outer sialic acids, to produce the corresponding gangliosides specifically O-acetylated in the sialic acid bound in alpha-2,3 and alpha-2,8 residues. We demonstrate here that O-acetylation occurred specifically in the C-9 position of the sialic acid. In summary, we present a new method of specific O-acetylation of ganglioside sialic acids that permits the large scale preparation of these modified glycosphingolipids, facilitating both, the study of their mechanism of antitumoral action and their use as therapeutic drugs for treating glioblastoma multiform (GBM) patients.

  6. Motor nerve damage is associated with anti-ganglioside antibodies in diabetes.

    PubMed

    Matà, Sabrina; Betti, Elisabetta; Masotti, Giulio; Pinto, Francesco; Lolli, Francesco

    2004-09-01

    Few reports exist on the association between the humoral immune response to glycolipids and neuropathic findings in diabetes. To address this issue, we assayed serum anti-GM1, GD1b, GD1a, and sulfatides IgG and IgM in a group of 85 non-selected diabetic patients, and correlated these antibodies to clinical and electrophysiological findings. Diabetic patients had higher mean titers of anti-GM1 (IgM), GD1b, GD1a, and sulfatide (IgG) antibodies when compared to healthy controls. Patients with a positive titer of anti-ganglioside antibodies had significant alterations of motor conduction parameters. The statistical significance increased when considering those patients with both anti-ganglioside reactivity and a high value for glycosylated hemoglobin. Production of antibodies to ganglioside may follow the exposure of hidden motor nerve epitopes in damaged motor nerves and contribute to the neuropathy.

  7. NGcGM3 Ganglioside: A Privileged Target for Cancer Vaccines

    PubMed Central

    Fernandez, Luis E.; Gabri, Mariano R.; Guthmann, Marcelo D.; Gomez, Roberto E.; Gold, Silvia; Fainboim, Leonardo; Gomez, Daniel E.; Alonso, Daniel F.

    2010-01-01

    Active specific immunotherapy is a promising field in cancer research. N-glycolyl (NGc) gangliosides, and particularly NGcGM3, have received attention as a privileged target for cancer therapy. Many clinical trials have been performed with the anti-NGc-containing gangliosides anti-idiotype monoclonal antibody racotumomab (formerly known as 1E10) and the conjugated NGcGM3/VSSP vaccine for immunotherapy of melanoma, breast, and lung cancer. The present paper examines the role of NGc-gangliosides in tumor biology as well as the available preclinical and clinical data on these vaccine products. A brief discussion on the relevance of prioritization of cancer antigens in vaccine development is also included. PMID:21048926

  8. Selection of ganglioside GM1-binding peptides by using a phage library.

    PubMed

    Matsubara, T; Ishikawa, D; Taki, T; Okahata, Y; Sato, T

    1999-08-06

    Ganglioside Gal beta1 --> 3GalNAc beta1 --> 4(NeuAc alpha2 --> 3) Gal beta1 --> 4Glc beta1 -->1'Cer (GM1)-binding peptides were obtained from a phage-displayed pentadecapeptide library by an affinity selection. The selection processes were in situ-monitored by a quartz-crystal microbalance method, on which a ganglioside GM1 monolayer was transferred. After five rounds of biopanning, the DNA sequencing of 18 selected phages showed that only three individual clones were selected. The peptide sequences of the random region were found to be DFRRLPGAFWQLRQP, GWWYKGRARPVSAVA and VWRLLAPPFSNRLLP. Binding constants of these phage clones to the GM1 monolayer were 10(10) M(-1). Three synthetic pentadecapeptides inhibited the binding of cholera toxin B subunit to the GM1 monolayer with an IC50 of 24, 13 and 1.0 microM, respectively. These peptides will be useful for searching functional roles of ganglioside GMI.

  9. Measuring the diffusion coefficient of ganglioside on cell membrane by fluorescence correlation spectroscopy

    NASA Astrophysics Data System (ADS)

    Dong, Shiqing; You, Minghai; Chen, Jianling; Zhou, Jie; Xie, Shusen; Yang, Hongqin

    2017-06-01

    The fluidity of proteins and lipids on cell membrane plays an important role in cell’s physiological functions. Fluorescence correlation spectroscopy (FCS) is an effective technique to detect the rapid dynamic behaviors of proteins and/or lipids in living cells. In this study, we used the rhodamine6G solution to optimize the FCS system. And, cholera toxin B subunit (CT-B) was used to label ganglioside on living Hela cell membranes. The diffusion time and coefficients of ganglioside can be obtained through fitting the autocorrelation curve based on the model of two-dimensional cell membrane. The results showed that the diffusion coefficients of ganglioside distributed within a wide range. It revealed the lateral diffusion of lipids on cell membrane was inhomogeneous, which was due to different microstructures of cytoplasmic membrane. The study provides a helpful method for further studying the dynamic characteristics of proteins and lipids molecules on living cell membrane.

  10. Differential subcellular localization of cholesterol, gangliosides, and glycosaminoglycans in murine models of mucopolysaccharide storage disorders.

    PubMed

    McGlynn, Robert; Dobrenis, Kostantin; Walkley, Steven U

    2004-12-20

    The mucopolysaccharidoses (MPSs) are a complex family of lysosomal storage disorders characterized by failure to degrade heparan sulfate (HS) and/or other types of glycosaminoglycans (GAGs) secondary to the absence of specific lysosomal enzymes. An accompanying storage of glycosphingolipids (GSLs), most notably GM2 and GM3 gangliosides, has also been documented to occur in many types of MPS disease and is believed to be caused by secondary inhibition of GSL-degradative enzymes by intracellular GAG accumulation. We have documented the presence of secondary ganglioside accumulation in mouse models of several MPS disorders (types I, IIIA, IIIB, and VII) and report that this storage is accompanied by sequestration of free cholesterol in a manner similar to that observed in primary gangliosidoses. Using confocal microscopy, we evaluated the cellular distribution of cholesterol, GM2 and GM3 gangliosides, and HS in brains of mice with MPS IIIA disease. Unexpectedly, we found that although both gangliosides often accumulated in the same neurons, they were consistently located in separate populations of cytoplasmic vesicles. Additionally, GM3 ganglioside only partially co-localized with the primary storage material (HS), and cholesterol likewise only partially co-localized with the GM2 and GM3 gangliosides. These findings raise significant questions about the mechanism(s) responsible for secondary accumulation of storage materials in MPS disease. Furthermore, given that GSLs and cholesterol are constituents of membrane rafts believed critical in signal transduction events in neurons, their co-sequestration in individual neurons suggests the presence of defects in the composition, trafficking, and/or recycling of raft components and thus possible new mechanisms to explain neuronal dysfunction in MPS disorders.

  11. Biosynthesis of the major brain gangliosides GD1a and GT1b.

    PubMed

    Sturgill, Elizabeth R; Aoki, Kazuhiro; Lopez, Pablo H H; Colacurcio, Daniel; Vajn, Katarina; Lorenzini, Ileana; Majić, Senka; Yang, Won Ho; Heffer, Marija; Tiemeyer, Michael; Marth, Jamey D; Schnaar, Ronald L

    2012-10-01

    Gangliosides-sialylated glycosphingolipids-are the major glycoconjugates of nerve cells. The same four structures-GM1, GD1a, GD1b and GT1b-comprise the great majority of gangliosides in mammalian brains. They share a common tetrasaccharide core (Galβ1-3GalNAcβ1-4Galβ1-4Glcβ1-1'Cer) with one or two sialic acids on the internal galactose and zero (GM1 and GD1b) or one (GD1a and GT1b) α2-3-linked sialic acid on the terminal galactose. Whereas the genes responsible for the sialylation of the internal galactose are known, those responsible for terminal sialylation have not been established in vivo. We report that St3gal2 and St3gal3 are responsible for nearly all the terminal sialylation of brain gangliosides in the mouse. When brain ganglioside expression was analyzed in adult St3gal1-, St3gal2-, St3gal3- and St3gal4-null mice, only St3gal2-null mice differed significantly from wild type, expressing half the normal amount of GD1a and GT1b. St3gal1/2-double-null mice were no different than St3gal2-single-null mice; however, St3gal2/3-double-null mice were >95% depleted in gangliosides GD1a and GT1b. Total ganglioside expression (lipid-bound sialic acid) in the brains of St3gal2/3-double-null mice was equivalent to that in wild-type mice, whereas total protein sialylation was reduced by half. St3gal2/3-double-null mice were small, weak and short lived. They were half the weight of wild-type mice at weaning and displayed early hindlimb dysreflexia. We conclude that the St3gal2 and St3gal3 gene products (ST3Gal-II and ST3Gal-III sialyltransferases) are largely responsible for ganglioside terminal α2-3 sialylation in the brain, synthesizing the major brain gangliosides GD1a and GT1b.

  12. Design and synthesis of a novel ganglioside ligand for influenza A viruses.

    PubMed

    Nohara, Tomohiro; Imamura, Akihiro; Yamaguchi, Maho; Hidari, Kazuya I P J; Suzuki, Takashi; Komori, Tatsuya; Ando, Hiromune; Ishida, Hideharu; Kiso, Makoto

    2012-08-10

    A novel ganglioside bearing Neua2-3Gal and Neua2-6Gal structures as distal sequences was designed as a ligand for influenza A viruses. The efficient synthesis of the designed ganglioside was accomplished by employing the cassette coupling approach as a key reaction, which was executed between the non-reducing end of the oligosaccharide and the cyclic glucosylceramide moiety. Examination of its binding activity to influenza A viruses revealed that the new ligand is recognized by Neua2-3 and 2-6 type viruses.

  13. Characterization of the cholera toxin receptor on Balb/c 3T3 cells as a ganglioside similar to, or identical with, ganglioside GM1. No evidence for galactoproteins with receptor activity.

    PubMed

    Critchley, D R; Streuli, C H; Kellie, S; Ansell, S; Patel, B

    1982-04-15

    Balb/c 3T3 cells contain a large number [(0.8-1.6) x 10(6)] of high-affinity (half-maximal binding at 0.2 nM) binding sites for cholera toxin that are resistant to proteolysis, but are quantitatively extracted with chloroform/methanol. The following evidence rigorously establishes that the receptor is a ganglioside similar to, or identical with, ganglioside GM1 by the galactose oxidase/NaB3H4 technique on intact cells was inhibited by cholera toxin. (2) Ganglioside GM1 was specifically adsorbed from Nonidet P40 extracts of both surface- (galactose oxidase/NaB3H4 technique) and metabolically ([1-14C]palmitate) labelled cells in the presence of cholera toxin, anti-toxin and Staphylococcus aureus. (3) Ganglioside GM1 was the only ganglioside labelled when total cellular gangliosides separated on silica-gel sheets were overlayed with 125I-labelled cholera toxin, although GM3 and GD1a were the major gangliosides present. In contrast no evidence for a galactoprotein with receptor activity was obtained. Cholera toxin did not protect the terminal galactose residues of cell-surface glycoproteins from labelling by the galactose oxidase/NaB3H4 technique. No toxin-binding proteins could be identified in Nonidet P40 extracts of [35S]-methionine-labelled cells by immunochemical means. After sodium dodecyl sulphate/polyacrylamide-gel electrophoresis none of the major cellular galactoproteins identified by overlaying gels with 125I-labelled ricin were able to bind 125I-labelled cholera toxin. It is concluded that the cholera toxin receptor on Balb/c 3T3 cells is exclusively ganglioside GM1 (or a related species), and that cholera toxin can therefore be used to probe the function and organisation of gangliosides in these cells as previously outlined [Critchley, Ansell, Perkins, Dilks & Ingram (1979) J. Supramol. Struct. 12, 273-291].

  14. Effect of tin ions on enhancing the intensity of narrow luminescence line at 311 nm of Gd3+ ions in Li2Osbnd PbOsbnd P2O5 glass system

    NASA Astrophysics Data System (ADS)

    Gandhi, Y.; Rajanikanth, P.; Sundara Rao, M.; Ravi Kumar, V.; Veeraiah, N.; Piasecki, M.

    2016-07-01

    This study is mainly focused on enriching the UVB 311 narrow emission band of Gd3+ ions in Li2Osbnd PbOsbnd P2O5 glasses doped with 1.0 mol% of Gd2O3 and mixed with different concentrations of SnO2 (0-7.0 mol%). The emission spectra SnO2 free glasses exhibited intense narrow UVB band at 311 nm due to 6P7/2 → 8S7/2 transition of Gd3+ ions when excited at 273 nm. The intensity of this band is found to be enhanced nearly four times when the glasses are mixed with 3.0 mol% of SnO2. The reasons for this enhancement have been explored in the light of energy transfer from Sn4+ to Gd3+ ions with the help of rate equations. The declustering of Gd3+ ions (that reduce cross relaxation losses) by tin ions is also found to the other reason for such enrichment. The 311 nm radiation is an efficient in the treatment of various skin diseases and currently it is one of the most desirable and commonly utilised UVB in the construction of phototherapy devices.

  15. Exchange interaction between Gd3+ and the conduction electron system in the normal state of GdχY1 - χBa2Cu3O7 - δ

    NASA Astrophysics Data System (ADS)

    Kessler, C.; Mehring, M.; Castellaz, P.; Borodi, G.; Filip, C.; Darabont, A.; Giurgiu, L. V.

    1997-01-01

    ESR-investigations of Gd 3+-ions in YBa 2Cu 3O 7-δ give distinct indications for an exchange coupling of these paramagnetic ions to the doped charge carriers. We analyse the spin dynamics in terms of the theory of metals and discuss the different contributions to the exchange interaction.

  16. Involvement of gangliosides in the suppression of the immune response: an explanation for the progression of UV-induced fibrosarcomas

    SciTech Connect

    Frey, J.L.

    1987-01-01

    Ultraviolet-irradiation-induced fibrosarcoma cells with either progressor or regressor properties were studied for structural differences in their glycosphingolipid (GSL) content and composition. UV-progressor tumor cells contained a ganglioside, G/sub Dla/, which the UV-regressor cells lacked. This ganglioside was found in the serum of tumor bearing animals and was shed from the UV-progressor tumor cells. In our analysis of the role gangliosides might play in the tumor progression, we found that both spent medium and crude ganglioside preparations from progressor UV-tumor cells inhibited the mitogenic proliferation of normal lymphocytes. In vitro analysis with purified preparations of G/sub Dla/ showed that this ganglioside had immunosuppressive properties in mitogen-stimulated cultures. The kinetics of the inhibition response showed that maximal inhibition occurred if G/sub Dla/ was present at the prereplicative stage of lymphocyte proliferation. If lymphocytes are precultured with G/sub Dla/, exogenous ganglioside could be removed without loss of the inhibitory activity on lymphocyte proliferation. These results suggest that the presence of the ganglioside, G/sub Dla/, on the cell surface of progressor tumors could alter an immune response

  17. Dissecting the Role of Anti-ganglioside Antibodies in Guillain-Barré Syndrome: an Animal Model Approach.

    PubMed

    Asthana, Pallavi; Vong, Joaquim Si Long; Kumar, Gajendra; Chang, Raymond Chuen-Chung; Zhang, Gang; Sheikh, Kazim A; Ma, Chi Him Eddie

    2016-09-01

    Guillain-Barré syndrome (GBS) is an autoimmune polyneuropathy disease affecting the peripheral nervous system (PNS). Most of the GBS patients experienced neurological symptoms such as paresthesia, weakness, pain, and areflexia. There are also combinations of non-neurological symptoms which include upper respiratory tract infection and diarrhea. One of the major causes of GBS is due largely to the autoantibodies against gangliosides located on the peripheral nerves. Gangliosides are sialic acid-bearing glycosphingolipids consisting of a ceramide lipid anchor with one or more sialic acids attached to a neutral sugar backbone. Molecular mimicry between the outer components of oligosaccharide of gangliosides on nerve membrane and lipo-oligosaccharide of microbes is thought to trigger the autoimmunity. Intra-peritoneal implantation of monoclonal ganglioside antibodies secreting hybridoma into animals induced peripheral neuropathy. Recent studies demonstrated that injection of synthesized anti-ganglioside antibodies raised by hybridoma cells into mice initiates immune response against peripheral nerves, and eventually failure in peripheral nerve regeneration. Accumulating evidences indicate that the conjugation of anti-ganglioside monoclonal antibodies to activating FcγRIII present on the circulating macrophages inhibits axonal regeneration. The activation of RhoA signaling pathways is also involved in neurite outgrowth inhibition. However, the link between these two molecular events remains unresolved and requires further investigation. Development of anti-ganglioside antagonists can serve as targeted therapy for the treatment of GBS and will open a new approach of drug development with maximum efficacy and specificity.

  18. Phosphatidylinositol 4-phosphate 5-kinase α is induced in ganglioside-stimulated brain astrocytes and contributes to inflammatory responses

    PubMed Central

    Kim, Bokyung; Yoon, Sarah; Kim, Yeon Joo; Liu, Tian; Woo, Joo Hong; Chwae, Yong-Joon; Joe, Eun-hye; Jou, Ilo

    2010-01-01

    In brain tissue, astrocytes play defensive roles in central nervous system integrity by mediating immune responses against pathological conditions. Type I phosphatidylinositol 4-phosphate 5-kinase α (PIP5Kα) that is responsible for production of p