27 results on '"Gd3 ganglioside"'
Search Results
2. Evidence for Ca2+-induced structural change in diluted GD3 ganglioside dispersions.
- Author
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Ejarque, Julia B., Duarte, Evandro L., Lamy, M. Teresa, and Rozenfeld, Julio H.K.
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ELECTRON paramagnetic resonance spectroscopy , *DISPERSION (Chemistry) , *DILUTION , *NEURODEGENERATION - Abstract
• GD3 is involved in cancer malignancy and neurodegenerative disorders. • DSC and EPR spectroscopy data indicate that GD3 forms micelles in dilute dispersions. • In presence of Ca2+, GD3 shows athermotropic behavior and a molecular rigidity typical of a lamellar structure. • The Ca2+-induced structural change may be relevant to the GD3 pathophysiological roles. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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3. Ganglioside GD3 regulates neural stem cell quiescence and controls postnatal neurogenesis.
- Author
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Fuchigami T, Itokazu Y, and Yu RK
- Subjects
- Mice, Animals, Neurogenesis physiology, Gangliosides genetics, Gangliosides metabolism, Cell Differentiation, Mice, Knockout, Neural Stem Cells metabolism
- Abstract
The postnatal neural stem cell (NSC) pool hosts quiescent and activated radial glia-like NSCs contributing to neurogenesis throughout adulthood. However, the underlying regulatory mechanism during the transition from quiescent NSCs to activated NSCs in the postnatal NSC niche is not fully understood. Lipid metabolism and lipid composition play important roles in regulating NSC fate determination. Biological lipid membranes define the individual cellular shape and help maintain cellular organization and are highly heterogeneous in structure and there exist diverse microdomains (also known as lipid rafts), which are enriched with sugar molecules, such as glycosphingolipids. An often overlooked but key aspect is that the functional activities of proteins and genes are highly dependent on their molecular environments. We previously reported that ganglioside GD3 is the predominant species in NSCs and that the reduced postnatal NSC pools are observed in global GD3-synthase knockout (GD3S-KO) mouse brains. The specific roles of GD3 in determining the stage and cell-lineage determination of NSCs remain unclear, since global GD3S-KO mice cannot distinguish if GD3 regulates postnatal neurogenesis or developmental impacts. Here, we show that inducible GD3 deletion in postnatal radial glia-like NSCs promotes NSC activation, resulting in the loss of the long-term maintenance of the adult NSC pools. The reduced neurogenesis in the subventricular zone (SVZ) and the dentate gyrus (DG) of GD3S-conditional-knockout mice led to the impaired olfactory and memory functions. Thus, our results provide convincing evidence that postnatal GD3 maintains the quiescent state of radial glia-like NSCs in the adult NSC niche., (© 2023 Wiley Periodicals LLC.)
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- 2024
- Full Text
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4. Influence of GM3 and GD3 glycolipids on the conductometric properties of a model membrane system
- Author
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Cametti, C., De Luca, F., Macri, M. A., Maraviglia, B., Misasi, R., Sorice, M., Kilian, H. -G., editor, Lagaly, G., editor, Laggner, P., editor, and Glatter, O., editor
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- 1993
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5. Antibody response to GD3 ganglioside is independent of NKT cells.
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Park, J.-E., Lu, S. X., Wu, D. Y., Prendes, M., and Chapman, P. B.
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CELLS , *GANGLIOSIDES , *GLYCOLIPIDS , *GLYCOCONJUGATES , *B cells , *IMMUNOGLOBULINS - Abstract
Background NKT cells recognize glycolipids presented by CD1d on antigen-presenting cells (APC) and have been largely characterized by their ability to be activated by α-galactosylceramide, a glycolipid not expressed on mammalian cells. We have shown previously that GD3 can be cross-presented by CD1d to NKT cells and is the first tumor-derived glycolipid recognized by NKT cells. But the ability of NKT cells to modulate B-cell responses to tumor glycolipids that are themselves recognized by NKT cells has not been explored. Methods We tested whether NKT cells are required for antibody (Ab) responses to GD3. We immunized wild-type mice, mice deficient in invariant chain NKT cells (iNKT cells) and mice deficient in total NKT cells against GD3. Ab titer against GD3 was measured by ELISA. Results We found the IgM and IgG responses against GD3 were similar among the three strains of mice, including the IgG isotypes induced. Pre-expanded NKT cells to GD3 did not affect the anti-GD3 Ab response. Discussion We conclude that Ab responses to GD3 are independent of NKT cells and that strategies to manipulate NKT cells in vivo are not likely to enhance the anti-GD3 Ab response induced by vaccines. [ABSTRACT FROM AUTHOR]
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- 2008
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6. Apoptosis of human breast carcinoma cells in the presence of cis-platin and L-/D-PPMP: IV. Modulation of replication complexes and glycolipid: Glycosyltransferases.
- Author
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Boyle, Patrick, Ma, Rui, Tuteja, Narendra, Banerjee, Sipra, and Basu, Subhash
- Abstract
Apoptosis of human breast carcinoma cells (SKBR-3, MCF-7, and MDA-468) has been observed after treatment of these cells with anti-cancer drug cis-platin and glycosphingolipid biosynthesis inhibitor L- and D-PPMP, respectively. These drugs initiated apoptosis in a dose-dependent manner as measured by phenotypic morphological changes, by binding of a fluorescent phophatidyl serine-specific dye (PSS-380) onto the outer leaflet of the cell membranes, and by activation of caspases, −3, −8, and −9. It was observed that in two hours very little apoptotic process had started but predominant biochemical changes occurred after 6 h. DNA degradation started after 24 hours of drug treatment. However, very little is known about the stability of the ‘`Replication Complexes’’ during the apoptotic process. DNA helicases are motor proteins that catalyze the melting of genomic DNA during its replication, repair, and recombination processes. Previously, DNA helicase-III was characterized as a component of the replication complexes isolated from embryonic chicken brains as well as breast and colon carcinoma cells. Helicase activities were measured by a novel method (ROME assay), and DNA polymerase-α activities were determined by regular chain extension of the nicked ACT-DNA, by determining values obtained from +/− aphidicolin-treated incubation mixtures. In all three breast carcinoma cell lines, a common trend was observed: a decrease of activities of DNA polymerase-α and Helicase III. A sharp decrease of activities of the glycolipid sialyltransferases: SAT-2 (CMP-NeuAc; GD3 α2-8 sialyltransferase) and SAT-4 (CMP-NeuAc: GM1a α2-3 sialyltransferase) was observed in the apoptotic carcinoma cells treated with L-PPMP compared with cis-platin. [ABSTRACT FROM AUTHOR]
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- 2006
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7. A phase II trial comparing five dose levels of BEC2 anti-idiotypic monoclonal antibody vaccine that mimics GD3 ganglioside
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Chapman, Paul B., Williams, Linda, Salibi, Nadia, Hwu, Wen-Jen, Krown, Susan E., and Livingston, Philip O.
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MONOCLONAL antibodies , *VACCINES , *CANCER , *PATIENTS - Abstract
In previous studies, we showed that immunization with 2.5 mg of BEC2, an anti-idiotypic MAb that mimics GD3 ganglioside, can induce antibodies against GD3 in approximately 25% of patients. In this trial, 50 melanoma patients at high risk for recurrence were randomly assigned to one of the five BEC2 dose levels (2.5 μg–10 mg) to determine if lower or higher BEC2 doses are more immunogenic. We also tested whether prolonged booster immunizations can enhance the anti-GD3 antibody response. All patients developed detectable IgG against BEC2 except for one patient at the lowest BEC2 dose level. Six patients developed detectable antibody responses to GD3, all of them at the lower three dose levels of BEC2. We conclude that high doses of BEC2 are not necessary to induce anti-GD3 antibody responses and that lower doses may be more immunogenic than the 2.5 mg dose used in previous BEC2 trials. Prolonged booster immunizations did not induce or maintain antibody responses. [Copyright &y& Elsevier]
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- 2004
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8. Mapping effector functions of a monoclonal antibody to GD3 by characterization of a mouse-human chimeric antibody.
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Chapman, Paul, Gillies, Stephen, Houghton, Alan, and Reilly, Regina
- Abstract
R24, a mouse monoclonal antibody against GD3 ganglioside, exhibits a wide range of in vitro effector functions. It also has the ability to bind to itself, presumably through homophilic Fab-Fab interactions, which have been proposed to contribute to its high relative avidity for GD3 and to its effector function activity. It is not known which of these characteristics is necessary for the antitumor effects observed in melanoma patients treated with R24. A mouse-human chimeric R24 (chR24) molecule has been constructed in which the GD3-binding site is preserved. Chimeric R24 demonstrates a lower level of binding to GD3 than does mouse R24 suggesting that there may be some differences between the GD3-binding sites of the two mAb or that Fc determinants can contribute to R24 avidity for GD3. The property of homophilic binding is retained by chR24, demonstrating formally that homophilic binding of R24 involves interactions between variable domains. Both R24 and chR24 fix human complement and mediate antibody-dependent cellular cytotoxicity although chR24 was slightly less efficient at the latter. Unlike R24, chR24 was not able to inhibit melanoma cell attachment to plastic surfaces and was not able to activate human T lymphocytes. We hypothesize that chR24 does not bind to GD3 with an avidity high enough to mediate these effector functions. [ABSTRACT FROM AUTHOR]
- Published
- 1994
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9. Intranasal infusion of GD3 and GM1 gangliosides downregulates alpha-synuclein and controls tyrosine hydroxylase gene in a PD model mouse.
- Author
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Itokazu Y, Fuchigami T, Morgan JC, and Yu RK
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- Administration, Intranasal, Animals, Cell Line, Disease Models, Animal, Down-Regulation, Epigenesis, Genetic drug effects, G(M1) Ganglioside pharmacology, Gangliosides pharmacology, Gene Expression Regulation drug effects, Humans, Male, Mice, Parkinson Disease genetics, Parkinson Disease metabolism, Substantia Nigra drug effects, Substantia Nigra enzymology, Tyrosine 3-Monooxygenase genetics, G(M1) Ganglioside administration & dosage, Gangliosides administration & dosage, Parkinson Disease drug therapy, Tyrosine 3-Monooxygenase metabolism, alpha-Synuclein metabolism
- Abstract
Parkinson's disease (PD) is characterized by Lewy bodies (composed predominantly of alpha-synuclein [aSyn]) and loss of pigmented midbrain dopaminergic neurons comprising the nigrostriatal pathway. Most PD patients show significant deficiency of gangliosides, including GM1, in the brain, and GM1 ganglioside appears to keep dopaminergic neurons functioning properly. Thus, supplementation of GM1 could potentially provide some rescuing effects. In this study, we demonstrate that intranasal infusion of GD3 and GM1 gangliosides reduces intracellular aSyn levels. GM1 also significantly enhances expression of tyrosine hydroxylase (TH) in the substantia nigra pars compacta of the A53T aSyn overexpressing mouse, following restored nuclear expression of nuclear receptor related 1 (Nurr1, also known as NR4A2), an essential transcription factor for differentiation, maturation, and maintenance of midbrain dopaminergic neurons. GM1 induces epigenetic activation of the TH gene, including augmentation of acetylated histones and recruitment of Nurr1 to the TH promoter region. Our data indicate that intranasal administration of gangliosides could reduce neurotoxic proteins and restore functional neurons via modulating chromatin status by nuclear gangliosides., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
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10. Progenitor/Stem Cell Markers in Brain Adjacent to Glioblastoma: GD3 Ganglioside and NG2 Proteoglycan Expression
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Lama, Gina, Mangiola, Annunziato, Proietti, Gabriella, Colabianchi, Anna, Angelucci, Cristiana, D'Alessio, A, De Bonis, Pasquale, Geloso, Maria Concetta, Lauriola, Libero, Binda, E, Biamonte, Filippo, Giuffrida, Mg, Vescovi, A, Sica, Gigliola, D'Alessio, Alessio, Lama, G, Mangiola, A, Proietti, G, Colabianchi, A, Angelucci, C, D'Alessio, A, De Bonis, P, Geloso, M, Lauriola, L, Binda, E, Biamonte, F, Giuffrida, M, Vescovi, A, and Sica, G
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0301 basic medicine ,Male ,Pathology ,Mice, SCID ,NG2 proteoglycan ,Stem cell marker ,Nestin ,angiogenesis ,Mice ,0302 clinical medicine ,Gangliosides ,GD3 ganglioside ,Brain adjacent to tumor ,Tumor ,biology ,Brain Neoplasms ,Sialyltransferase ,Stem Cells ,General Medicine ,Middle Aged ,Immunohistochemistry ,Neurology ,Antigen ,030220 oncology & carcinogenesis ,lipids (amino acids, peptides, and proteins) ,Female ,Proteoglycans ,Settore BIO/17 - ISTOLOGIA ,Stem cell ,Human ,Adult ,medicine.medical_specialty ,glioblastoma,Brain adjacent to tumor, Cancer stem cells, GD3 ganglioside, NG2 proteoglycan ,SCID ,Pathology and Forensic Medicine ,NO ,Brain Neoplasm ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Young Adult ,Cancer stem cell ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,Actins ,Aged ,Antigens ,Brain Chemistry ,Glioblastoma ,Karnofsky Performance Status ,Sialyltransferases ,Actin ,Progenitor ,proteoglycan ,Settore MED/08 - ANATOMIA PATOLOGICA ,Animal ,stem cell ,030104 developmental biology ,Proteoglycan ,nervous system ,Ganglioside ,biology.protein ,Karnofsky Performance Statu ,Neurology (clinical) ,Biomarkers - Abstract
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 (α-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.
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- 2016
11. Abstract A73: GD3 ganglioside-enriched extracellular vesicles stimulate melanocyte migration
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Andréia Hanada Otake, Roger Chammas, Ana Paula M. Duarte, Renata de Freitas Saito, and Alexandre F. Ramos
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Cancer Research ,Gd3 ganglioside ,Oncology ,Chemistry ,Extracellular vesicles ,Melanocyte migration ,Cell biology - Abstract
Gangliosides are sialic acid-containing glycosphingolipids located mainly in outlet membrane plasma. Tumors usually accumulate gangliosides as disialoganglioside GD3 which is widely expressed in melanomas and neuroblastomas. GD3 has been associated with tumor progression, conferring tumorigenic characteristics to cells such as increased proliferation and migration. In order to investigate the role of GD3 in cell migration, we have transfected the GD3 synthase gene (ST8Sia I) in a melanocyte cell line. In this work we have demonstrated that overexpression of GD3 upon transfection of GD3 synthase was associated with an increased migratory response towards laminin-1. GD3 and 9-O-acetyl-GD3 gangliosides, which colocalize with integrins in cell lamellipodia, are positive modulators of integrin function in the migratory response while GD3 was left behind as a molecular footprint. Indeed, addition of exogenous GD3 to the cells stimulated cell migration whereas exogenously added GM3 inhibited it. However, depletion of gangliosides using a glucosylceramide synthase inhibitor led cells more migratory. Glycosphingolipids content modulates FGF-2-induced cell migration as we demonstrated that FGF-2 induces cell migration. However, this effect was abolished after using glucosylceramide synthase inhibitor, suggesting that GD3 may modulate the motogenic activity of FGF-2. Finally, we showed that GD3 synthase transfected melanocytes release extracellular vesicles (EVs) enriched in GD3. These EVs are responsible for modulating cell migration response due to increase average velocity of GD3 negative cells as we showed in a real-time wound-healing assay. This study shows that EVs from a subset of GD3 positive cells may contribute to the horizontal signaling propagation to a different subset of GD3 negative cells. Thus, data present here led us to an important insight into how EVs carrying GD3 ganglioside could participate in intercellular communication modulating cellular migration. Citation Format: Andreia H. Otake, Ana Paula M. Duarte, Renata de Freitas Saito, Alexandre F. Ramos, Roger Chammas. GD3 ganglioside-enriched extracellular vesicles stimulate melanocyte migration [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A73.
- Published
- 2018
12. Molecular mimicry of phage displayed peptides mimicking GD3 ganglioside
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Soldano Ferrone, Jörg Willers, Darja Kanduc, Alberta Lucchese, Willers, J, Lucchese, Alberta, Kanduc, D, and Ferrone, S.
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Physiology ,medicine.drug_class ,medicine.medical_treatment ,Molecular Sequence Data ,Endogeny ,Cross Reactions ,Biology ,medicine.disease_cause ,Monoclonal antibody ,Biochemistry ,Homology (biology) ,Cell Line ,Cellular and Molecular Neuroscience ,Endocrinology ,Antigen ,Gangliosides ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Bacteriophages ,Amino Acid Sequence ,Cloning, Molecular ,Melanoma-associated antigen ,Gd3 ganglioside ,Molecular Mimicry ,Antibodies, Monoclonal ,Immunotherapy ,Molecular mimicry ,lipids (amino acids, peptides, and proteins) ,Peptides - Abstract
We have analyzed sequence homologies between nonimmunogenic phage displayed peptides mimicking GD3 ganglioside and human/mouse self-proteins. The GD3 ganglioside phagotopes showed homology to proteins involved in carbohydrate metabolism/transport. Besides this expected homology, molecular mimicry of critical regulatory proteins was found. These data contribute to our understanding of the structural relatedness of antigenic determinants defined by specific anti-GD3 monoclonal antibodies and, in addition, suggest that molecular mimicry might explain the nonimmunogenicity of these peptides otherwise characterized by specificity to the mAb counterpart. We conclude that construction of peptides harboring motifs absent or scarcely represented in endogenous self-proteins might be a useful approach in melanoma immunotherapy.
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- 1999
13. [Untitled]
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Laura Mauri, Sandro Sonnino, Riccardo Casellato, and Gunther Kirschner
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chemistry.chemical_classification ,Gd3 ganglioside ,Chromatography ,Ganglioside ,Chemistry ,Glycoconjugate ,GM1-lactone ,Cell Biology ,Nuclear magnetic resonance spectroscopy ,Biochemistry ,Hydrolysis ,Ganglioside GM3 ,Yield (chemistry) ,Molecular Biology - Abstract
A simple procedure is described for preparing GM3 ganglioside, from a few milligrams to grams, from GM1-lactone (Sonnino et al., (1985) Glycoconjugate J 2: 343-54) [1]. The synthesis was carried out under the following optimal conditions: 30 mM GM1-lactone in 0.25 M H2SO4 in DMSO, 30 min, 70 degrees C, nitrogen atmosphere, strong stirring. The yield of GM3 was 55%. The procedure applied to milligram amounts of GD1b-dilactone gave GD3 ganglioside.
- Published
- 1999
14. Intracellular mediators of programmed cell death initiated at the cell surface receptor Fas
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Condo, I. and Testi, R.
- Published
- 2000
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15. Detection of GD3 ganglioside in primary melanomas depends on histopathologic procedures used for tumor preservation
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Debarbieux, S., Popa, I., Luc Thomas, Kanitakis, J., Pirot, F., Portoukalian, J., and Haftek, M.
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melanoma ,GD3 ganglioside ,immunohistochemistry ,retrospective study ,Immunoenzyme Techniques ,Skin Neoplasms ,Biopsy ,Gangliosides ,Cytological Techniques ,Feasibility Studies ,Frozen Sections ,Humans ,Reproducibility of Results ,Melanoma ,Chromatography, High Pressure Liquid ,Retrospective Studies - Abstract
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.
- Published
- 2009
16. BIOENGINEERING OF SURFACE GD3 GANGLIOSIDE ON HUMAN MELANOMA CELLS FOR IMMUNOTARGETING
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Michel Gilbert, Silvia Borrelli, Wei Zou, Harold J. Jennings, Tianmin Liu, and Robert Pon
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Gd3 ganglioside ,Chemistry ,Cancer research ,Human melanoma - Published
- 2002
17. Involvement of caspase-3 and GD3 ganglioside in ceramide-induced apoptosis in Farber disease
- Author
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Giorgio Stassi, Giovanni Zummo, Giovanni Peri, Felicia Farina, Fabio Bucchieri, Matilde Todaro, Francesco Cappello, Farina, F., Cappello, F., Todaro, M., Bucchieri, F., Peri, G., Zummo, G., and Stassi, G
- Subjects
Adult ,Ceramide ,Pathology ,medicine.medical_specialty ,Histology ,Colon ,Caspase 3 ,Apoptosis ,Ceramides ,chemistry.chemical_compound ,Gangliosides ,medicine ,GD3 ganglioside ,Humans ,Intestinal Mucosa ,Caspase ,Farber disease ,TUNEL assay ,biology ,Apoptosi ,Cell Biology ,medicine.disease ,Ceramidase ,K18 ,Epithelium ,Active caspase-3 ,Lysosomal Storage Diseases ,medicine.anatomical_structure ,chemistry ,Caspases ,Cancer research ,biology.protein ,Anatomy - Abstract
Farber's disease (FD) is a rare genetic disorder caused by ceramidase deficiency, which results in ceramide accumulation in lung, liver, colon, skeletal muscle, cartilage, and bone. Although this disease has been symptomatically characterized, little is known about its molecular pathogenetic process. Because recent studies reported that ceramide accumulation induces GD3 ganglioside formation and apoptosis, we investigated, in tissue obtained via colonoscopy from seriously involved patients, the possible involvement of ceramide in FD colonocyte destruction. Histochemical and TUNEL analyses of paraffin-embedded sections revealed that 45 ± 4.3% of FD colonocytes showed morphological signs of apoptosis compared with the 8 ± 2.3% of constitutive epithelial cell death. Importantly, immunohistochemical study for pro-apoptotic factors showed that GD3 accumulation co-localized with active caspase-3 and cleaved K18 in FD colon tissue. These findings provide evidence for a role of the apoptotic ceramide pathway in the pathogenesis of FD.
- Published
- 2000
18. The role of ceramide in receptor- and stress-induced apoptosis studied in acidic ceramidase-deficient Farber disease cells
- Author
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Burek, C. J., Roth, J., Koch, H. G., Harzer, K., Los, Marek Jan, Schulze-Osthoff, Klaus, Burek, C. J., Roth, J., Koch, H. G., Harzer, K., Los, Marek Jan, and Schulze-Osthoff, Klaus
- Abstract
The activation of sphingomyelinases leading to the generation of ceramide has been implicated in various apoptotic pathways. However, the role of ceramide as an essential death mediator remains highly controversial. In the present study, we investigated the functional relevance of ceramide in a genetic model by using primary cells from a Farber disease patient. These cells accumulate ceramide as the result of an inherited deficiency of acidic ceramidase. We demonstrate that Farber disease lymphocytes and fibroblasts underwent apoptosis induced by various stress stimuli, including staurosporine, anticancer drugs and gamma -irradiation, equally as normal control cells. In addition, caspase activation by these proapoptotic agents occurred rather similarly in Farber disease and control fibroblasts. Interestingly, Farber disease lymphoid cells underwent apoptosis induced by the CD95 death receptor more rapidly than control cells. Our data therefore suggest that ceramide does not play an essential role as a second messenger in stress-induced apoptosis. However, in accordance with a role in lipid-rich microdomains, ceramide by altering membrane composition may function as an amplifier in CD95-mediated apoptosis.
- Published
- 2001
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19. Clinical Studies with Anti-Idiotypic Monoclonal Antibody BEC2 that Mimics GD3 Ganglioside
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Paul B. Chapman
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Gd3 ganglioside ,Anti-idiotypic Monoclonal Antibody BEC2 ,business.industry ,Immunology ,Medicine ,business - Published
- 1997
20. 1P197 Structure of GD3 Ganglioside/Cholesterol Mixture Depending on Temperature and Salts
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Tomohiro Hayakawa, Harutaka Hirai, Kohji Kasahara, N. Suzuki, Mitsuhiro Hirai, and Kohei Yuyama
- Subjects
chemistry.chemical_compound ,Gd3 ganglioside ,Chromatography ,Chemistry ,Cholesterol - Published
- 2004
21. GD3 ganglioside mediates programmed cell death triggered by CD95 (Fas/APO-1) and ceramide
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Barbara Tomassini, F. D' Agostino, Luisa Lenti, Ann Zeuner, Maria Rita Rippo, R De Maria, Florence Malisan, and Roberto Testi
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Ceramide ,chemistry.chemical_compound ,Programmed cell death ,Gd3 ganglioside ,Chemistry ,Immunology ,Immunology and Allergy ,Fas apo 1 ,Fas receptor ,Cell biology - Published
- 1997
22. 136 Isolation and characterization of human melanoma cell lines deficient in GD3 ganglioside expression
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B.K. Mohan-Raj, Chidori Asagami, Kenneth O. Lloyd, and Junji Nakano
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Gd3 ganglioside ,Cell culture ,Human melanoma ,Dermatology ,Biology ,Isolation (microbiology) ,Molecular Biology ,Biochemistry ,Molecular biology - Published
- 1996
23. The biological significance and role of GD3 ganglioside in U-1242MG glioma cells
- Author
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Omran, Ola Mahmoud F.
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- Health Sciences, Pathology, GD3 ganglioside, Gliomas, Apoptosis, Caspase-8, DR5
- Abstract
Human glioblastoma multiforme (GBM) is the most common malignant glioma in adults. GBM constitutes a major problem in clinical management due to its high infiltrative ability, resistance to the current cancer therapy that account for its bad prognosis. Specific target molecules produced in the cells are required to control the biology of malignant glioma cells and facilitate the treatment strategies. Many reports demonstrated that exogenous addition of the disialoganglioside GD3 induces apoptosis in various cell types, acting mainly through the mitochondrion. The overall aim of this work is to elucidate the biological roles of endogenously synthesized GD3 on U-1242MG glioblastoma cell line. We conducted experiments to elucidate the biological effects of endogenous GD3 expression on U-1242MG cells, and the results of these showed that the expression of GD3 was associated with apoptosis. After establishing that GD3 causes apoptosis, we investigated some of the mechanisms leading to apoptosis that are induced by three death ligands (FasL, TNF-α and TRAIL). We found that of the three death ligands only TRAIL-induced apoptosis in U-1242MG cells. We also found that three death receptors (DR5, Fas and TNF-R1) involved in the early stage of apoptosis are located in the caveolin-1 enriched fractions. Furthermore, TRAIL initiates the subcellular relocalization of several death receptors and other apoptotic molecules. We found that endogenously expressed GD3 is localized in the caveolae of U42-GRD2 cells, and that GD3 expression induced translocation of the death receptors Fas, TNF-R1, DR5 and other apoptotic molecules such as caspase-8 into the caveolae as a part of the molecular mechanism of GD3-induced apoptosis. Moreover, in contrast to caspase-8, the subcellular localization of cytochrome c was not affected by endogenous GD3 expression indicating that the mitochondrial pathway leading to apoptosis was probably not involved. From the above we conclude that the endogenous expression of GD3 induces apoptosis in U-1242MG glioma cells mediated through the extrinsic, not the intrinsic pathway.
- Published
- 2004
24. Isolation and characterization of GD3 ganglioside having a novel disialosyl residue from rabbit thymus
- Author
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M Iwamori and Y Nagai
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Ceramide ,Gd3 ganglioside ,biology ,Chemistry ,Cell Biology ,Biochemistry ,Sialic acid ,Trisialoganglioside ,chemistry.chemical_compound ,Residue (chemistry) ,Methylation analysis ,biology.protein ,Molecular Biology ,Neuraminidase - Abstract
A major component of the di- and trisialoganglioside fraction of rabbit thymus was isolated. By neuraminidase treatment, methylation analysis, and CrO3 oxidation, it was identified as GD3 ganglioside with the novel disialosyl residue, NeuNGlyc(alpha, 2-8)NeuNAc(alpha, 2-3)Gal-(beta, 1-4)Glc(beta, 1-1)ceramide. Its concentration was 21.92 nmol/g of wet tissue (12.10% of the total gangliosides) and it contained 91.52% of the lipid-bound sialic acid in di- and trisialogangliosides of rabbit thymus.
- Published
- 1978
25. Analysis of cellular expression of gangliosides by gene transfection. I: GD3 expression in myc-transfected and transformed 3Y1 correlates with anchorage-independent growth activity
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Yoshitaka Nagai, Hitoshi Nakaishi, Kazuko Shiroki, and Yutaka Sanai
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viruses ,Biophysics ,Biology ,Transfection ,Biochemistry ,Cell Line ,chemistry.chemical_compound ,Soft agar ,Gangliosides ,Animals ,Molecular Biology ,Gd3 ganglioside ,Cell Biology ,Oncogenes ,Embryo, Mammalian ,Molecular biology ,Rats ,Transformation (genetics) ,Cell Transformation, Neoplastic ,chemistry ,Cell culture ,lipids (amino acids, peptides, and proteins) ,Anchorage-Independent Growth ,DNA ,Cell Division - Abstract
Transfection of c- myc DNA into rat fibroblastic 3Y1 cell line resulted in the neosynthesis of GD3 ganglioside, as has been previously shown to occur after transfection of 3Y1 cells with adeno E1 (Nakakuma, H., Sanai, Y., Shiroki, K., and Nagai, Y. (1984) J. Biochem. 96, 1471–1480); in both cases, the products are expressed intranuclearly. Moreover, a clear correlation was identified between levels of GD3 expression and colony-forming activity (in soft agar) of myc -transformed 3Y1 cells, implying that GD3 plays some specific role in myc -induced transformation of 3Y1 cell line.
- Published
- 1988
26. GD3 ganglioside: A marker for the diagnosis and treatment of neuroectodermal tumors?
- Author
-
Hans-Peter Dienes, W. Dippld, K H Meyer zum Büschenfelde, and Alexander Knuth
- Subjects
Cancer Research ,medicine.medical_specialty ,Pathology ,Gd3 ganglioside ,Hematology ,Oncology ,business.industry ,Internal medicine ,medicine ,General Medicine ,business - Published
- 1986
27. Expression Cloning of a CMP-NeuAc:NeuAcα2-3Galβ1-4Glc$\beta$1-1'Cer α2, 8-Sialyltransferase (GD3 Synthase) from Human Melanoma Cells
- Author
-
Nara, Kiyomitsu, Watanabe, Yumiko, Maruyama, Kazuo, Kasahara, Kohji, Nagai, Yoshitaka, and Sanai, Yutaka
- Published
- 1994
Catalog
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