Base de dados : MEDLINE
Pesquisa : D02.065.313.425 [Categoria DeCS]
Referências encontradas : 561 [refinar]
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[PMID]:28428058
[Au] Autor:Zheng S; Eierhoff T; Aigal S; Brandel A; Thuenauer R; de Bentzmann S; Imberty A; Römer W
[Ad] Endereço:Faculty of Biology, Schänzlestraße 1, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Schänzlestraße 18, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
[Ti] Título:The Pseudomonas aeruginosa lectin LecA triggers host cell signalling by glycosphingolipid-dependent phosphorylation of the adaptor protein CrkII.
[So] Source:Biochim Biophys Acta;1864(7):1236-1245, 2017 07.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The human pathogen Pseudomonas aeruginosa induces phosphorylation of the adaptor protein CrkII by activating the non-receptor tyrosine kinase Abl to promote its uptake into host cells. So far, specific factors of P. aeruginosa, which induce Abl/CrkII signalling, are entirely unknown. In this research, we employed human lung epithelial cells H1299, Chinese hamster ovary cells and P. aeruginosa wild type strain PAO1 to study the invasion process of P. aeruginosa into host cells by using microbiological, biochemical and cell biological approaches such as Western Blot, immunofluorescence microscopy and flow cytometry. Here, we demonstrate that the host glycosphingolipid globotriaosylceramide, also termed Gb3, represents a signalling receptor for the P. aeruginosa lectin LecA to induce CrkII phosphorylation at tyrosine 221. Alterations in Gb3 expression and LecA function correlate with CrkII phosphorylation. Interestingly, phosphorylation of CrkII occurs independently of Abl kinase. We further show that Src family kinases transduce the signal induced by LecA binding to Gb3, leading to Crk phosphorylation. In summary, we identified LecA as a bacterial factor, which utilizes a so far unrecognized mechanism for phospho-CrkII induction by binding to the host glycosphingolipid receptor Gb3. The LecA/Gb3 interaction highlights the potential of glycolipids to mediate signalling processes across the plasma membrane and should be further elucidated to gain deeper insights into this non-canonical mechanism of activating host cell processes.
[Mh] Termos MeSH primário: Adesinas Bacterianas/metabolismo
Globosídeos/metabolismo
Proteínas Proto-Oncogênicas c-crk/metabolismo
Pseudomonas aeruginosa/patogenicidade
Transdução de Sinais
Triexosilceramidas/metabolismo
[Mh] Termos MeSH secundário: Animais
Células CHO
Linhagem Celular
Cricetinae
Cricetulus
Interações Hospedeiro-Patógeno
Seres Humanos
Fosforilação
Processamento de Proteína Pós-Traducional
Pseudomonas aeruginosa/metabolismo
Mucosa Respiratória/metabolismo
Mucosa Respiratória/microbiologia
Quinases da Família src/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adhesins, Bacterial); 0 (Globosides); 0 (LecA protein, bacteria); 0 (Proto-Oncogene Proteins c-crk); 0 (Trihexosylceramides); 0 (globotrihexosylceramide); EC 2.7.10.2 (src-Family Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170422
[St] Status:MEDLINE


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[PMID]:28194794
[Au] Autor:Kawai M; Obara K; Onodera T; Enomoto T; Ogasawara K; Tsuneyama H; Uchikawa M; Inaba S
[Ad] Endereço:Japanese Red Cross Kanto-Koshinetsu Block Saitama Blood Center, Saitama, Japan.
[Ti] Título:Mutations of the KLF1 gene detected in Japanese with the In(Lu) phenotype.
[So] Source:Transfusion;57(4):1072-1077, 2017 Apr.
[Is] ISSN:1537-2995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In(Lu) is characterized by a reduced expression of antigens in the Lutheran blood group system as well as other blood group antigens. Mutations of the erythroid transcription factor, KLF1, have been reported to cause the In(Lu) phenotype, and we investigated Japanese In(Lu) to estimate the prevalence of the phenotype and KLF1 polymorphism. STUDY DESIGN AND METHODS: Blood samples were screened by monoclonal anti-CD44 and the In(Lu) phenotype was confirmed by tube tests including adsorption and elution tests using anti-Lu and anti-Lu . KLF1, LU, and A4GALT genes were analyzed by polymerase chain reaction and sequencing. RESULTS: We identified 100 of 481,322 blood donors (0.02%), and the previously characterized 20 donors, who had the In(Lu) phenotype with the LUB/LUB genotype. A total of 100 of the 120 In(Lu) individuals had mutant KLF1 alleles, and we identified 13 known and 21 novel alleles. The mutant KLF1 alleles with c.947G>A (p.Cys316Tyr), c.862A>G (p.Lys288Glu), or c.968C>G (p.Ser323Trp) were major in the In(Lu) individuals. The P1 antigen of 29 In(Lu) (two P /P , 27 P /P ) showed significantly weakened expression by hemagglutination. CONCLUSIONS: The prevalence of the In(Lu) phenotype in the Japanese population was 0.02%, and we identified 13 known and 21 novel KLF1 alleles. The KLF1 mutations cause the reduced expression of the P1 antigen.
[Mh] Termos MeSH primário: Moléculas de Adesão Celular/genética
Fatores de Transcrição Kruppel-Like/genética
Sistema do Grupo Sanguíneo Lutheran/genética
Mutação de Sentido Incorreto
Fenótipo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Grupo com Ancestrais do Continente Asiático
Moléculas de Adesão Celular/sangue
Feminino
Galactosiltransferases/biossíntese
Galactosiltransferases/genética
Globosídeos/biossíntese
Globosídeos/metabolismo
Seres Humanos
Japão
Fatores de Transcrição Kruppel-Like/sangue
Sistema do Grupo Sanguíneo Lutheran/sangue
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BCAM protein, human); 0 (Cell Adhesion Molecules); 0 (Globosides); 0 (Kruppel-Like Transcription Factors); 0 (Lutheran Blood-Group System); 0 (erythroid Kruppel-like factor); 0 (galactopyranosyl-1-4-paragloboside); EC 2.4.1.- (Galactosyltransferases); EC 2.4.1.- (UDP-galactose-lactosylceramide alpha 1-4-galactosyltransferase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170621
[Lr] Data última revisão:
170621
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170215
[St] Status:MEDLINE
[do] DOI:10.1111/trf.13990


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[PMID]:27973758
[Au] Autor:Lubkowski J; Durbin SV; Silva MC; Farnsworth D; Gildersleeve JC; Oliva ML; Wlodawer A
[Ad] Endereço:Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
[Ti] Título:Structural analysis and unique molecular recognition properties of a Bauhinia forficata lectin that inhibits cancer cell growth.
[So] Source:FEBS J;284(3):429-450, 2017 Feb.
[Is] ISSN:1742-4658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Lectins have been used at length for basic research and clinical applications. New insights into the molecular recognition properties enhance our basic understanding of carbohydrate-protein interactions and aid in the design/development of new lectins. In this study, we used a combination of cell-based assays, glycan microarrays, and X-ray crystallography to evaluate the structure and function of the recombinant Bauhinia forficata lectin (BfL). The lectin was shown to be cytostatic for several cancer cell lines included in the NCI-60 panel; in particular, it inhibited growth of melanoma cancer cells (LOX IMVI) by over 95%. BfL is dimeric in solution and highly specific for binding of oligosaccharides and glycopeptides with terminal N-acetylgalactosamine (GalNAc). BfL was found to have especially strong binding (apparent K  = 0.5-1.0 nm) to the tumor-associated Tn antigen. High-resolution crystal structures were determined for the ligand-free lectin, as well as for its complexes with three Tn glycopeptides, globotetraose, and the blood group A antigen. Extensive analysis of the eight crystal structures and comparison to structures of related lectins revealed several unique features of GalNAc recognition. Of special note, the carboxylate group of Glu126, lining the glycan-binding pocket, forms H-bonds with both the N-acetyl of GalNAc and the peptide amido group of Tn antigens. Stabilization provided by Glu126 is described here for the first time for any GalNAc-specific lectin. Taken together, the results provide new insights into the molecular recognition of carbohydrates and provide a structural understanding that will enable rational engineering of BfL for a variety of applications. DATABASE: Structural data are available in the PDB under the accession numbers 5T50, 5T52, 5T55, 5T54, 5T5L, 5T5J, 5T5P, and 5T5O.
[Mh] Termos MeSH primário: Antígenos Glicosídicos Associados a Tumores/metabolismo
Antineoplásicos Fitogênicos/química
Bauhinia/química
Lectinas de Plantas/química
[Mh] Termos MeSH secundário: Acetilgalactosamina/química
Acetilgalactosamina/metabolismo
Antígenos Glicosídicos Associados a Tumores/química
Antineoplásicos Fitogênicos/isolamento & purificação
Antineoplásicos Fitogênicos/farmacologia
Sítios de Ligação
Antígenos de Grupos Sanguíneos/química
Antígenos de Grupos Sanguíneos/metabolismo
Linhagem Celular Tumoral
Clonagem Molecular
Cristalografia por Raios X
Dimerização
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Globosídeos/química
Globosídeos/metabolismo
Glicopeptídeos/química
Glicopeptídeos/metabolismo
Seres Humanos
Ligações de Hidrogênio
Cinética
Modelos Moleculares
Oligossacarídeos/química
Oligossacarídeos/metabolismo
Extratos Vegetais/química
Lectinas de Plantas/isolamento & purificação
Lectinas de Plantas/farmacologia
Ligação Proteica
Domínios e Motivos de Interação entre Proteínas
Estrutura Secundária de Proteína
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Tumor-Associated, Carbohydrate); 0 (Antineoplastic Agents, Phytogenic); 0 (Blood Group Antigens); 0 (Globosides); 0 (Glycopeptides); 0 (Oligosaccharides); 0 (Plant Extracts); 0 (Plant Lectins); 0 (Recombinant Proteins); 0 (Tn antigen); 75660-79-6 (globotetraose); KM15WK8O5T (Acetylgalactosamine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170620
[Lr] Data última revisão:
170620
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161216
[St] Status:MEDLINE
[do] DOI:10.1111/febs.13989


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[PMID]:27344728
[Au] Autor:Ito A; Kawasaki Y; Kakoi N; Shimada S; Saito S; Arai Y
[Ti] Título:[Disialosyl globopentaosylceramide (DSGb5) as a biomarker of prostate cancer].
[So] Source:Nihon Rinsho;74 Suppl 3:196-200, 2016 May 20.
[Is] ISSN:0047-1852
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Mh] Termos MeSH primário: Globosídeos/análise
Neoplasias da Próstata/diagnóstico
[Mh] Termos MeSH secundário: Globosídeos/química
Globosídeos/genética
Seres Humanos
Células Matadoras Naturais/imunologia
Masculino
Neovascularização Patológica
Neoplasias da Próstata/irrigação sanguínea
Neoplasias da Próstata/química
RNA Interferente Pequeno/genética
Recidiva
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Globosides); 0 (RNA, Small Interfering); 60267-39-2 (Forssman glycolipid)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160628
[St] Status:MEDLINE


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[PMID]:26685676
[Au] Autor:Chan YS; Ng TB
[Ad] Endereço:School of Biomedical Sciences, Lo Kwee Seong Integrated Biomedical Sciences Building, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. bomberharo@yahoo.com.hk.
[Ti] Título:Shiga toxins: from structure and mechanism to applications.
[So] Source:Appl Microbiol Biotechnol;100(4):1597-610, 2016 Feb.
[Is] ISSN:1432-0614
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Shiga toxins are a group of type 2 ribosome-inactivating proteins (RIPs) produced in several types of bacteria. The toxins possess an AB5 structure, which comprises a catalytic A chain with N-glycosidase activity, and five identical B chains and recognize and bind to the target cells with specific carbohydrate moieties. In humans, the major molecular target which recognizes the Shiga toxins is the Gb3 receptor, which is mainly expressed on the cell surface of endothelial cells of the intestine, kidney, and the brain. This causes these organs to be susceptible to the toxicity of Shiga toxins. When a person is infected by Shiga toxin-producing bacteria, the toxin is produced in the gut, translocated to the circulatory system, and carried to the target cells. Toxicity of the toxin causes inflammatory responses and severe cell damages in the intestine, kidneys, and brain, bringing about the hemolytic uremic syndrome (HUS), which can be fatal. The Shiga toxin requires a couple of steps to exert its toxicity to the target cells. After binding with the target cell surface receptor, the toxin requires a complicated process to be transported into the cytosol of the cell before it can approach the ribosomes. The mechanisms for the interactions of the toxin with the cells are described in this review. The consequences of the toxin on the cells are also discussed. It gives an overview of the steps for the toxin to be produced and transported, expression of catalytic activity, and the effects of the toxin on the target cells, as well as effects on the human body.
[Mh] Termos MeSH primário: Globosídeos/metabolismo
Inibidores da Síntese de Proteínas/metabolismo
Inibidores da Síntese de Proteínas/toxicidade
Toxinas Shiga/metabolismo
Toxinas Shiga/toxicidade
Triexosilceramidas/metabolismo
[Mh] Termos MeSH secundário: Encéfalo/efeitos dos fármacos
Encéfalo/patologia
Células Endoteliais/efeitos dos fármacos
Seres Humanos
Intestinos/efeitos dos fármacos
Intestinos/patologia
Rim/efeitos dos fármacos
Rim/patologia
Inibidores da Síntese de Proteínas/química
Transporte Proteico
Ribossomos/efeitos dos fármacos
Toxinas Shiga/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Globosides); 0 (Protein Synthesis Inhibitors); 0 (Shiga Toxins); 0 (Trihexosylceramides); 0 (globotrihexosylceramide)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151222
[St] Status:MEDLINE
[do] DOI:10.1007/s00253-015-7236-3


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[PMID]:26464281
[Au] Autor:Steil D; Schepers CL; Pohlentz G; Legros N; Runde J; Humpf HU; Karch H; Müthing J
[Ad] Endereço:Institutes for Hygiene University of Münster, D-48149 Münster, Germany.
[Ti] Título:Shiga toxin glycosphingolipid receptors of Vero-B4 kidney epithelial cells and their membrane microdomain lipid environment.
[So] Source:J Lipid Res;56(12):2322-36, 2015 Dec.
[Is] ISSN:1539-7262
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Shiga toxins (Stxs) are produced by enterohemorrhagic Escherichia coli (EHEC), which cause human infections with an often fatal outcome. Vero cell lines, derived from African green monkey kidney, represent the gold standard for determining the cytotoxic effects of Stxs. Despite their global use, knowledge about the exact structures of the Stx receptor glycosphingolipids (GSLs) and their assembly in lipid rafts is poor. Here we present a comprehensive structural analysis of Stx receptor GSLs and their distribution to detergent-resistant membranes (DRMs), which were prepared from Vero-B4 cells and used as lipid raft equivalents. We identified globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer) as the GSL receptors for Stx1a, Stx2a, and Stx2e subtypes using TLC overlay detection combined with MS. The uncommon Stx receptor, globopentaosylceramide (Gb5Cer, Galß3GalNAcß3Galα4Galß4Glcß1Cer), which was specifically recognized (in addition to Gb3Cer and Gb4Cer) by Stx2e, was fully structurally characterized. Lipoforms of Stx receptor GSLs were found to mainly harbor ceramide moieties composed of sphingosine (d18:1) and C24:0/C24:1 or C16:0 fatty acid. Moreover, co-occurrence with lipid raft markers, SM and cholesterol, in DRMs suggested GSL association with membrane microdomains. This study provides the basis for further exploring the functional impact of lipid raft-associated Stx receptors for toxin-mediated injury of Vero-B4 cells.
[Mh] Termos MeSH primário: Glicoesfingolipídeos/metabolismo
Microdomínios da Membrana/metabolismo
Receptores de Superfície Celular/metabolismo
[Mh] Termos MeSH secundário: Animais
Cercopithecus aethiops
Células Epiteliais/metabolismo
Globosídeos/metabolismo
Rim/citologia
Toxina Shiga/metabolismo
Triexosilceramidas/metabolismo
Células Vero
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Globosides); 0 (Glycosphingolipids); 0 (Receptors, Cell Surface); 0 (Trihexosylceramides); 0 (shigella toxin receptor); 11034-93-8 (globotetraosylceramide); 60267-39-2 (Forssman glycolipid); 71965-57-6 (globotriaosylceramide); 75757-64-1 (Shiga Toxin)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151015
[St] Status:MEDLINE
[do] DOI:10.1194/jlr.M063040


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[PMID]:26423148
[Au] Autor:Cameron G; Pellicci DG; Uldrich AP; Besra GS; Illarionov P; Williams SJ; La Gruta NL; Rossjohn J; Godfrey DI
[Ad] Endereço:Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia;
[Ti] Título:Antigen Specificity of Type I NKT Cells Is Governed by TCR ß-Chain Diversity.
[So] Source:J Immunol;195(10):4604-14, 2015 Nov 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:NKT cells recognize lipid-based Ags presented by CD1d. Type I NKT cells are often referred to as invariant owing to their mostly invariant TCR α-chain usage (Vα14-Jα18 in mice, Vα24-Jα18 in humans). However, these cells have diverse TCR ß-chains, including Vß8, Vß7, and Vß2 in mice and Vß11 in humans, joined to a range of TCR Dß and Jß genes. In this study, we demonstrate that TCR ß-chain composition can dramatically influence lipid Ag recognition in an Ag-dependent manner. Namely, the glycolipids α-glucosylceramide and isoglobotrihexosylceramide were preferentially recognized by Vß7(+) NKT cells from mice, whereas the α-galactosylceramide analog OCH, with a truncated sphingosine chain, was preferentially recognized by Vß8(+) NKT cells from mice. We show that the influence of the TCR ß-chain is due to a combination of Vß-, Jß-, and CDR3ß-encoded residues and that these TCRs can recapitulate the selective Ag reactivity in TCR-transduced cell lines. Similar observations were made with human NKT cells where different CDR3ß-encoded residues determined Ag preference. These findings indicate that NKT TCR ß-chain diversity results in differential and nonhierarchical Ag recognition by these cells, which implies that some Ags can preferentially activate type I NKT cell subsets.
[Mh] Termos MeSH primário: Antígenos CD1d/imunologia
Genes Codificadores da Cadeia beta de Receptores de Linfócitos T/genética
Glucosilceramidas/imunologia
Ativação Linfocitária/imunologia
Células T Matadoras Naturais/imunologia
Receptores de Antígenos de Linfócitos T alfa-beta/genética
[Mh] Termos MeSH secundário: Animais
Variação Genética/genética
Globosídeos/imunologia
Seres Humanos
Lipídeos/imunologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Triexosilceramidas/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, CD1d); 0 (CD1d antigen, mouse); 0 (Globosides); 0 (Glucosylceramides); 0 (Lipids); 0 (Receptors, Antigen, T-Cell, alpha-beta); 0 (Trihexosylceramides); 0 (isoglobotrihexosylceramide)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:151002
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1501222


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[PMID]:26099582
[Au] Autor:Paton AW; Chen AY; Wang H; McAllister LJ; Höggerl F; Mayr UB; Shewell LK; Jennings MP; Morona R; Lubitz W; Paton JC
[Ad] Endereço:Research Centre for Infectious Diseases, Department of Molecular and Cellular Biology, University of Adelaide, Adelaide, South Australia, Australia.
[Ti] Título:Protection against Shiga-Toxigenic Escherichia coli by Non-Genetically Modified Organism Receptor Mimic Bacterial Ghosts.
[So] Source:Infect Immun;83(9):3526-33, 2015 Sep.
[Is] ISSN:1098-5522
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Shiga-toxigenic Escherichia coli (STEC) causes severe gastrointestinal infections in humans that may lead to life-threatening systemic sequelae, such as the hemolytic uremic syndrome (HUS). Rapid diagnosis of STEC infection early in the course of disease opens a window of opportunity for therapeutic intervention, for example, by administration of agents that neutralize Shiga toxin (Stx) in the gut lumen. We previously developed a recombinant bacterium that expresses a mimic of the Stx receptor globotriaosyl ceramide (Gb3) on its surface through modification of the lipopolysaccharide (A. W. Paton, R. Morona, and J. C. Paton, Nat Med 6:265-270, 2000, http://dx.doi.org/10.1038/73111). This construct was highly efficacious in vivo, protecting mice from otherwise fatal STEC disease, but the fact that it is a genetically modified organism (GMO) has been a barrier to clinical development. In the present study, we have overcome this issue by development of Gb3 receptor mimic bacterial ghosts (BGs) that are not classified as GMOs. Gb3-BGs neutralized Stx1 and Stx2 in vitro with high efficiency, whereas alternative Gb3-expressing non-GMO subbacterial particles (minicells and outer membrane blebs) were ineffective. Gb3-BGs were highly efficacious in a murine model of STEC disease. All mice (10/10) treated with Gb3-BGs survived challenge with a highly virulent O113:H21 STEC strain and showed no pathological signs of renal injury. In contrast, 6/10 mice treated with control BGs succumbed to STEC challenge, and survivors exhibited significant weight loss, neutrophilia, and histopathological evidence of renal damage. Thus, Gb3-BGs offer a non-GMO approach to treatment of STEC infection in humans, particularly in an outbreak setting.
[Mh] Termos MeSH primário: Infecções por Escherichia coli/prevenção & controle
Globosídeos/imunologia
Mimetismo Molecular
Triexosilceramidas/imunologia
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Feminino
Camundongos
Camundongos Endogâmicos BALB C
Organismos Geneticamente Modificados
Escherichia coli Shiga Toxigênica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Globosides); 0 (Trihexosylceramides); 0 (globotrihexosylceramide)
[Em] Mês de entrada:1511
[Cu] Atualização por classe:160301
[Lr] Data última revisão:
160301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150624
[St] Status:MEDLINE
[do] DOI:10.1128/IAI.00669-15


  9 / 561 MEDLINE  
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[PMID]:26055721
[Au] Autor:Westman JS; Benktander J; Storry JR; Peyrard T; Hult AK; Hellberg Å; Teneberg S; Olsson ML
[Ad] Endereço:From the Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, SE-22184 Lund, Sweden.
[Ti] Título:Identification of the Molecular and Genetic Basis of PX2, a Glycosphingolipid Blood Group Antigen Lacking on Globoside-deficient Erythrocytes.
[So] Source:J Biol Chem;290(30):18505-18, 2015 Jul 24.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The x2 glycosphingolipid is expressed on erythrocytes from individuals of all common blood group phenotypes and elevated on cells of the rare P/P1/P(k)-negative p blood group phenotype. Globoside or P antigen is synthesized by UDP-N-acetylgalactosamine:globotriaosyl-ceramide 3-ß-N-acetylgalactosaminyltransferase encoded by B3GALNT1. It is the most abundant non-acid glycosphingolipid on erythrocytes and displays the same terminal disaccharide, GalNAcß3Gal, as x2. We encountered a patient with mutations in B3GALNT1 causing the rare P-deficient P1 (k) phenotype and whose pretransfusion plasma was unexpectedly incompatible with p erythrocytes. The same phenomenon was also noted in seven other unrelated P-deficient individuals. Thin-layer chromatography, mass spectrometry, and flow cytometry were used to show that the naturally occurring antibodies made by p individuals recognize x2 and sialylated forms of x2, whereas x2 is lacking on P-deficient erythrocytes. Overexpression of B3GALNT1 resulted in synthesis of both P and x2. Knockdown experiments with siRNA against B3GALNT1 diminished x2 levels. We conclude that x2 fulfills blood group criteria and is synthesized by UDP-N-acetylgalactosamine: globotriaosylceramide 3-ß-N-acetylgalactosaminyltransferase. Based on this linkage, we proposed that x2 joins P in the GLOB blood group system (ISBT 028) and is renamed PX2 (GLOB2). Thus, in the absence of a functional P synthase, neither P nor PX2 are formed. As a consequence, naturally occurring anti-P and anti-PX2 can be made. Until the clinical significance of anti-PX2 is known, we also recommend that rare P1 (k) or P2 (k) erythrocyte units are preferentially selected for transfusion to P(k) patients because p erythrocytes may pose a risk for hemolytic transfusion reactions due to their elevated PX2 levels.
[Mh] Termos MeSH primário: Antígenos de Grupos Sanguíneos/genética
Dissacarídeos/genética
Eritrócitos/metabolismo
Glicoesfingolipídeos/genética
N-Acetilgalactosaminiltransferases/genética
[Mh] Termos MeSH secundário: Anticorpos/genética
Anticorpos/imunologia
Antígenos de Grupos Sanguíneos/imunologia
Antígenos de Grupos Sanguíneos/metabolismo
Eritrócitos/imunologia
Eritrócitos/patologia
Globosídeos/metabolismo
Glicoesfingolipídeos/biossíntese
Seres Humanos
Mutação
N-Acetilgalactosaminiltransferases/metabolismo
Fenótipo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies); 0 (Blood Group Antigens); 0 (Disaccharides); 0 (Globosides); 0 (Glycosphingolipids); 0 (N-acetylgalactosaminyl-1-3-galactose); EC 2.4.1.- (B3GALNT1 protein, human); EC 2.4.1.- (N-Acetylgalactosaminyltransferases)
[Em] Mês de entrada:1510
[Cu] Atualização por classe:160724
[Lr] Data última revisão:
160724
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150610
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M115.655308


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[PMID]:25864532
[Au] Autor:Kawasaki Y; Ito A; Kakoi N; Shimada S; Itoh J; Mitsuzuka K; Arai Y
[Ad] Endereço:Department of Urology, Tohoku University Graduate School of Medicine.
[Ti] Título:Ganglioside, disialosyl globopentaosylceramide (DSGb5), enhances the migration of renal cell carcinoma cells.
[So] Source:Tohoku J Exp Med;236(1):1-7, 2015 05.
[Is] ISSN:1349-3329
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:About one third of renal cell carcinoma (RCC) patients exhibit metastasis upon initial presentation. However, the molecular basis for RCC metastasis is not fully understood. A ganglioside, disialosyl globopentaosylceramide (DSGb5), was originally isolated from RCC tissue extracts, and its expression is correlated with RCC metastatic potential. DSGb5 is synthesized by GalNAc α2,6-sialyltransferase VI (ST6GalNAcVI) and is expressed on the surface of RCC cells. Importantly, DSGb5 binds to sialic acid-binding Ig-like lectin-7 (Siglec-7) expressed on natural killer (NK) cells, thereby inhibiting NK-cell cytotoxicity. However, the role of DSGb5 in RCC progression remains obscure. To address this issue, we used ACHN cells derived from malignant pleural effusion of a patient with metastatic RCC. Using the limiting dilution method, we isolated three independent clones with different DSGb5 expression levels. Comparison of these clones indicated that the cloned cells with high DSGb5 expression levels exhibited greater migration potential, compared to the clone with low DSGb5 expression levels. In contrast, DSGb5 expression levels exerted no significant effect on cell proliferation. We then established the ACHN-derived cell lines that stably expressed siRNA against ST6GalNAcVI mRNA or control siRNA. Importantly, the ST6GalNAcVI-knockdown cells expressed low levels of DSGb5. We thus demonstrated the significantly decreased migration potential of the ST6GalNAcVI-knockdown cells with low DSGb5 expression levels, compared to the control siRNA-transfected cells expressing high DSGb5 levels, but no significant difference in the cell proliferation. Thus, DSGb5 expression may ensure the migration of RCC cells. We propose that DSGb5 expressed on RCC cells may determine their metastatic capability.
[Mh] Termos MeSH primário: Carcinoma de Células Renais/metabolismo
Carcinoma de Células Renais/patologia
Movimento Celular
Globosídeos/metabolismo
Neoplasias Renais/metabolismo
Neoplasias Renais/patologia
[Mh] Termos MeSH secundário: Carcinoma de Células Renais/genética
Linhagem Celular Tumoral
Proliferação Celular
Separação Celular
Citometria de Fluxo
Regulação Neoplásica da Expressão Gênica
Globosídeos/química
Seres Humanos
Neoplasias Renais/genética
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DSGb5 compound); 0 (Globosides); 0 (RNA, Messenger); 60267-39-2 (Forssman glycolipid)
[Em] Mês de entrada:1601
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150414
[St] Status:MEDLINE
[do] DOI:10.1620/tjem.236.1



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