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Lewis X (lewi + x)
Kinds of Lewis X Selected AbstractsC-Disaccharides as Probes for Carbohydrate Recognition , Investigation of the Conformational Requirements for Binding of Disaccharide Mimetics of Sialyl Lewis XEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 4 2007Richard W. Denton Abstract A set of C-disaccharide analogs was designed to probe the recognition of a known O-disaccharide mimetic of sialyl Lewis X, to P-selectin. The synthesis of the C-glycosides centered on the de novo construction of the galactose residue via an oxocarbenium ion/enol ether cyclization. Conformational analysis was performed by a combination of NMR spectroscopy and molecular mechanics (MM) and molecular dynamics (MD) calculations. The inhibition of P-selectin binding was evaluated in a P-selectin Biacore assay. At 12 mM, the O-glycoside showed 48,% inhibition of binding, while the C-glycoside analogs exhibited between 25,31,% inhibition. This data is discussed within the context of the active conformation of sLex and the conformational behavior of these ligands. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] IPSE/alpha-1, a major secretory glycoprotein antigen from schistosome eggs, expresses the Lewis X motif on core-difucosylated N-glycansFEBS JOURNAL, Issue 10 2006Manfred Wuhrer Schistosomes are parasitic flatworms that infect millions of people in (sub)tropical areas around the world. Glycoconjugates of schistosomes play a critical role in the interaction of the different developmental stages of the parasite with the host. In particular, glycosylated components of the eggs produced by the adult worm pairs living in the bloodstream are strongly immunogenic. We have investigated the glycosylation of interleukin-4-inducing factor from schistosome eggs (IPSE/alpha-1), a major secretory egg antigen from Schistosoma mansoni that triggers interleukin-4 production in human basophils, by MS analysis of tryptic glycopeptides. Nanoscale LC-MS(/MS) and MALDI-TOF(/TOF)-MS studies combined with enzymatic degradations showed that monomeric IPSE/alpha-1 contains two N-glycosylation sites, which are each occupied for a large proportion with core-difucosylated diantennary glycans that carry one or more Lewis X motifs. Lewis X has been reported as a major immunogenic glycan element of schistosomes. This is the first report both on the expression of Lewis X on a specific schistosome egg protein and on a protein-specific glycosylation analysis of schistosome eggs. [source] Insulin/protein kinase B signalling pathway upregulates metastasis-related phenotypes and molecules in H7721 human hepatocarcinoma cell lineFEBS JOURNAL, Issue 18 2003Hui-Ling Qi The effect of insulin on cancer metastatic potential was studied in a human hepatocarcinoma cell line, H7721. Cell adhesion to human umbilical vein endothelial cells (HUVECs) and laminin as well as chemotactic cell migration and invasion were selected as the indices of metastasis-related phenotypes for assessment of metastatic potential ex vivo. The results indicated that insulin enhanced all of these metastasis-related phenotypes. After the cells were treated with specific inhibitor of PI3K (LY294002) or transfected with antisense cDNA of PKB (AS-PKB), all of the above phenotypes were attenuated, and they could not be significantly stimulated by insulin, indicating that the insulin effect on metastatic potential was mediated by PI3K and PKB. Only the monoclonal antibody to the sialyl Lewis X (SLex), but not antibodies to other Lewis antigens, significantly blocked the cell adhesion to HUVECs, cell migration and invasion, suggesting that SLex played a crucial role in the metastatic potential of H7721 cells. The upregulation of cell surface SLex and ,-1,3-fucosyltransferase-VII (,-1,3 Fuc T-VII, enzyme for SLex synthesis) was also mediated by PI3K and PKB, since LY294002 and AS-PKB also reduced the expressions of SLex and ,-1,3 FucT-VII, and attenuated the response to insulin. Furthermore, the alterations in the expressions of PKB protein and activity were correlated to the changes of metastatic phenotypes and SLex expression. Taken together, the insulin/PKB signalling pathway participated in the enhancement of metastatic potential of H7721 cells, which was mediated by the upregulation of the expression of SLex and ,-1,3 FucT-VII. [source] Transfection of the c- erbB2/neu gene upregulates the expression of sialyl Lewis X, ,1,3-fucosyltransferase VII, and metastatic potential in a human hepatocarcinoma cell lineFEBS JOURNAL, Issue 12 2001Fei Liu The pCMV4 plasmid containing the cancer-promoting gene, c- erbB2/neu, was cotransfected into the human hepatocarcinoma cell line 7721 with the pcDNA3 vector, which contains the ,neo' selectable marker. Several clones showing stable expression of c- erbB2/neu were established and characterized by determination of c- erbB2/neu mRNA and its encoded protein p185. Expression of Lewis antigens and ,1,3-fucosyltransferases and the biological behavior of 7721 cells after c- erbB2/neu transfection were studied using mock cells transfected with the vectors pCMV4 and pcDNA3 as controls. SLex expression on the surface of mock cells was high, whereas expression of SDLex, Lex and SLea was absent or negligible. This is compatible with the abundant expression of ,1,3-fucosyltransferase VII, very low expression of ,fucosyltransferase III/VI, and almost absent expression of ,1,3-fucosyltransferase IV in the mock cells. After transfection of c- erbB2/neu, expression of SLex and ,1,3-fucosyltransferase VII were simultaneously elevated, but that of ,fucosyltransferase III/VI was not altered. The expression of both SLex and ,1,3-fucosyltransferase VII correlated positively with the expression of c- erbB2/neu in different clones, being highest in clone 13, medium in clone 6, and lowest in clone 7. In addition, the adhesion of 7721 cells to human umbilical vein endothelial cells (HUVECs) or P-selectin, as well as cell migration and invasion, were increased in c- erbB2/neu -transfected cells. These increases also correlated positively with the expression intensities of c- erbB2/neu, SLex and ,1,3-fucosyltransferase VII in the different clones, whereas cell adhesion to fibronectin correlated negatively with these variables. mAbs to SLex (KM93) and SDLex (FH6) significantly and slightly, respectively, abolished cell adhesion to HUVECs or P-selectin and cell migration and invasion. mAbs to SDLex and SLea did not suppress cell adhesion to HUVECs nor inhibit cell migration and invasion. Transfection of ,1,3-fucosyltransferase VII cDNA into 7721 cells showed similar results to transfection of c- erbB2/neu, and the increased adhesion to HUVECs, cell migration, and invasion were also inhibited significantly by KM93 and slightly by FH6. These results indicate that expression of ,1,3-fucosyltransferase VII and its specific product, SLex, and their capacity for cell adhesion, migration and invasion are closely related. Therefore, the c- erbB2/neu gene is proposed to be a metastasis-promoting gene, and its effects are at least partially mediated by the increased expression of ,1,3-fucosyltransferase VII and SLex. [source] New Nonhydrolyzable Mimetics of Sialyl Lewis X and Their Binding Affinity to P-SelectinHELVETICA CHIMICA ACTA, Issue 5 2004Frédéric Carrel Wittig olefination of (2S,3R,5S,6R)-5-(acetyloxy)-tetrahydro-6-[(methoxymethoxy)methyl]-3-(phenylthio)- 2H -pyran-2-acetaldehyde ((+)- 10) with {2-[(2S,3R,4R,5R,6S)-tetrahydro-3,4,5-tris(methoxymethoxy)-6-methyl- 2H -pyran-2-yl]ethyl}triphenylphosphonium iodide ((,)- 11) gave a (Z)-alkene derivative (+)- 12 that was converted into (,R,2R,3S,4R,5R,6S)-tetrahydro- ,,3-dihydroxy-2-(hydroxymethyl)-5-(phenylthio)-6-{(2Z)-4-[(2S,3S,4R,5S,6S)-tetrahydro-3,4,5-trihydroxy-6-methyl-2H -pyran-2-yl]but-2-enyl}2H -pyran-4-acetic acid (8), (,R,2R,3S,4R,6S)-tetrahydro- ,,3-dihydroxy-2-(hydroxymethyl)-6-{4-[(2S,3S,4R,5S,6S)-tetrahydro-3,4,5-trihydroxy-6-methyl-2H -pyran-2-yl]butyl}-2H -pyran-4-acetic acid (9), and simpler analogues without the hydroxyacetic side chain such as (2S,3S,4R,5S,6S)-tetrahydro-6-methyl-2-{(2Z)-4-[(2S,3R,5S,6R)-tetrahydro-5-hydroxy-6-(hydroxymethyl)-3-(phenylthio)-2H -pyran-2-yl]but-2-enyl}-2H -pyran-3,4,5-triol (30), (2S,3S,4R,5S,6S)-tetrahydro-6-methyl-2-{[(2S,5S,6R)-tetrah dro-5-hydroxy-6-(hydroxymethyl)-2H -pyran-2-yl]butyl}-2H -pyran-3,4,5- triol ((,)- 41) and (2S,3S,4R,5S,6S)-tetrahydro-6-methyl-2-{(2Z/E))-4-[(2R,5S,6R)-tetrahydro-5-hydroxy-6-(hydroxymethyl)-2H -pyran-2-yl]but-2-enyl}-2H -pyran-3,4,5-triol (43). The key intermediates (+)- 10 and (,)- 11 were derived from isolevoglucosenone and from L -fucose, respectively. The following IC50 values were measured in a ELISA test for the affinities of sialyl Lewis x tetrasaccharide, 8, 9, 30, (,)- 41, and 43 toward P-selectin: 0.7, 2.5,2.8, 7.3,8.0, 5.3,5.9, 5.0,5.2, and 3.4,4.1,mM, respectively. [source] ,1,3 fucosyltransferase-VII up-regulates the mRNA of ,5 integrin and its biological functionJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2008Qiu-yan Wang Abstract After transfection of ,1,3fucosyltransferase (FucT)-VII cDNA into H7721 human hepatocarcinoma cells, the expression of ,5, but not ,1 integrin was significantly up-regulated. This was evidenced by the increase of ,5 integrin on cell surface as well as the increase of ,5 mRNA and protein in the cells. However, the expressions of sialyl Lewis X (SLex, the product of ,1,3FucT-VII) on both ,5 and ,1 integrin subunits were unchanged. Concomitantly, the tyrosine autophosphorylated FAK and dephosphorylated Src (FAK and Src involve in the signal transduction of integrin ,5,1) were up-regulated, while the Tyr-527 phosphorylated Src was down-regulated. The above-mentioned alterations were correlated to the expressions of ,1,3FucT-VII in different ,1,3FucT-VII transfected H7721 cell lines. In addition, after ,1,3FucT-VII transfection, cell adhesion to fibronectin (Fn) and chemotaxic cell migration were obviously promoted. The cell adhesion could be blocked by ,5 integrin antibody, and cell migration was obviously attenuated by the antibodies to both ,5 integrin and SLex. These findings suggest that the increased surface ,5 integrin caused by the up-regulation of ,5 mRNA promotes the cell adhesion to Fn, cell migratiom, and Fn-induced signaling of ,5,1 integrin. The up-regulation of surface SLex originated from the over expression of ,1,3FucT-VII also led to the stimulation of cell migration. This is the first time to report that ,1,3FucT-VII can regulate the mRNA expression of integrin. J. Cell. Biochem. 104: 2078,2090, 2008. © 2008 Wiley-Liss, Inc. [source] Glycosylation of liver acute-phase proteins in pancreatic cancer and chronic pancreatitisPROTEOMICS - CLINICAL APPLICATIONS, Issue 4 2010Ariadna Sarrats Abstract Purpose: Glycosylation of acute-phase proteins (APP), which is partially regulated by cytokines, may be distinct in disease and provide useful tumour markers. Thus, we have examined the glycosylation of major serum APP in pancreatic cancer (PaC), chronic pancreatitis (CP) and control patients. Experimental design: Using a specific anti-sialyl Lewis X antibody and N -glycan sequencing, we have determined glycosylation changes on ,-1-acid glycoprotein (AGP), haptoglobin (HPT), fetuin (FET), ,-1-antitrypsin (AT) and transferrin (TRF). Results: Increased levels of sialyl Lewis X (SLex) were detected on AGP in advanced PaC and CP and on HPT, FET, AT and TRF in CP. An increase in N -glycan branching was detected on AGP and HPT in the advanced stage of PaC and CP and on FET and TRF in the CP. A core fucosylated structure was increased on AGP and HPT only in the advanced PaC patients. Conclusions and clinical relevance: Changes in APP SLex and branching are probably associated with an inflammatory response because they were detected in both advanced PaC and CP patients and these conditions give rise to inflammation. On the contrary, the increase in APP core fucosylation could be cancer associated and the presence of this glycoform may give an advantage to the tumour. [source] Antibody microarray analysis of serum glycans in esophageal squamous cell carcinoma cases and controlsPROTEOMICS - CLINICAL APPLICATIONS, Issue 8 2009Changxia Shao Abstract The objective of this study was to characterize specific serum glycan profile in esophageal squamous cell carcinoma (ESCC) cases and matched controls. A recently developed lectin-based antibody array was applied to detect various cancer-associated glycotopes in sera from 23 cases and 23 controls. Glycan levels were highly expressed in sera of ESCC patients as compared with controls. These included fucosylation level on interleukin (IL) 8; mannose level on haptoglobin; N-acetylglucosamine levels on IL6, mucin (MUC)1, and von Willebrand factor (vWf); sialyl Lewis a (sLea) levels on blood group Lewis X, IL6, IL10, MUC1, and serum amyloid A (SAA); sialyl Tn antigen (sTn) levels on cathepsin D, gelsolin, IL10, and vWf; T antigen levels on IL8, IL10, blood group Lewis X, vitronectin, and vWf (p<0.05). In addition, receiver-operating characteristics (ROC) analysis showed significantly discriminal improvement between cases and controls as measured by area under ROC curve. The highest sum of sensitivity and specificity was 1.52 for carbohydrate antigen 19-9 detection on both MUC1 and SAA, with area under ROC curves of 0.73 and 0.71, respectively. Taken together, this lectin-based antibody microarray allows efficient profiling of variations in specific glycans on proteins in ESCC cases as compared with controls, some of which might be useful for clinical diagnosis, early detection, and/or treatment. [source] ChemInform Abstract: Diboronic Acids as Fluorescent Probes for Cells Expressing Sialyl Lewis XCHEMINFORM, Issue 49 2002Wenqian Yang Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Endothelial L-selectin ligand expression in nasal polypsALLERGY, Issue 1 2010F. A. Ebbens Abstract Background:, L-selectins on leukocytes and their counter-receptors on endothelial cells have been shown to be involved in leukocyte recruitment in chronic rhinosinusitis without nasal polyps (NP). Objectives:, The purpose of this study was to evaluate the expression level of functionally active endothelial L-selectin ligands in NP obtained from patients with NP of different etiology [simple NP, antro-choanal polyps (ACP) and cystic fibrosis (CF) NP] and inferior turbinate specimens of healthy controls and to compare these levels to the presence of various leukocyte subsets. Methods:, Nasal polyp specimens and healthy nasal mucosa specimens were obtained from patients undergoing surgery and were immunohistochemically stained with monoclonal antibodies detecting CD34, sialyl Lewis x (sLex) of sulfated extended core 1 lactosamines and various leukocyte subsets. Results:, All NP are characterized by a decrease in the number of CD34+ vessels. The number of eosinophils and the percentage of vessels expressing endothelial sulfated sLex epitopes is upregulated in all groups of simple NP. Tissue eosinophilia is increased in those patients with increased disease severity (acetyl salicylic acid intolerance), but the percentage of endothelial sulfated sLex epitopes is not. Results on CF NP are similar to those observed for simple NP. Antro-choanal polyps, on the contrary, are characterized by low numbers of tissue eosinophils and relatively few vessels expressing endothelial sulfated sLex epitopes. Conclusions:, Our results suggest that functionally active L-selectin ligands might play a role in guiding leukocyte traffic into NP in patients with simple NP and CF NP but not ACP. [source] | |||||||||||||