The role of DNA methylation in ST6Gal1 expression in gliomas
The mechanism of transcriptional silencing of ST6Gal1 in gliomas has not yet been elucidated. Multiple independent promoters govern the expression of the ST6Gal I gene. Here, we investigated whether epigenetic abnormalities involving DNA methylation affect ST6Gal1 expression. Transcript-specific qRT-PCR following exposure of glioma cell lines to 5-aza-2’-deoxycytidine (5-aza-dC), a DNA methyltransferase inhibitor, resulted in the re-expression of the normally quiescent ST6Gal1 mRNA driven exclusively by the P3 promoter sequence. The P3 promoter-specific transcription start site (TSS) was delineated by primer extensio...
Source: Glycobiology - December 4, 2016 Category: Biology Authors: Kroes, R. A., Moskal, J. R. Tags: Cancer Biology Source Type: research
Society for Glycobiology Awards - 2016
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Source: Glycobiology - December 4, 2016 Category: Biology Tags: Glyco-Forum Section Source Type: research
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Source: Glycobiology - December 4, 2016 Category: Biology Tags: Cover/Standing Material Source Type: research
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Source: Glycobiology - December 4, 2016 Category: Biology Tags: Cover/Standing Material Source Type: research
Oligosaccharides from the 3-linked 2-sulfated alpha-L-fucan and alpha-L-galactan show similar conformations but different dynamics
Here we have performed an nuclear magnetic resonance-based study on the ring and chain conformations as well as dynamics of oligosaccharides generated by acid hydrolysis on two structurally related glycans, a 3-linked 2-sulfated alpha-L-galactan and a 3-linked 2-sulfated alpha-L-fucan. Results derived from scalar couplings have confirmed the 1C4 chair configuration to both alpha-L-fucose and alpha-L-galactose, and a similar solution 3D structure for the oligosaccharide chains of both sulfated glycans as seen on the basis of NOE patterns. Measurements of spin-relaxation rates have suggested, however, a slight difference dyn...
Source: Glycobiology - November 21, 2016 Category: Biology Authors: Queiroz, I. N. L., Vilela-Silva, A.-C. E. S., Pomin, V. H. Tags: Structural Biology Source Type: research
Development of N- and O-linked oligosaccharide engineered Saccharomyces cerevisiae strain
Yeast cells have been engineered for the production of glycoproteins as biopharmaceuticals with humanized N-linked oligosaccharides. The suppression of yeast-specific O-mannosylation is important to reduce immune response and to improve heterologous protein productivity in the production of biopharmaceuticals. However, so far, there are few reports of the engineering of both N-linked and O-linked oligosaccharides in yeast cells. In the present study, we describe the generation of a Saccharomyces cerevisiae strain capable of producing a glycoprotein with humanized Man5GlcNAc2 N-linked oligosaccharides, an intermediate of ma...
Source: Glycobiology - November 21, 2016 Category: Biology Authors: Abe, H., Tomimoto, K., Fujita, Y., Iwaki, T., Chiba, Y., Nakayama, K.-i., Nakajima, Y. Tags: Microbial Biology Source Type: research
Introduction of H-antigens into oligosaccharides and sugar chains of glycoproteins using highly efficient 1,2-{alpha}-L-fucosynthase
In this study, we succeeded in derivatizing inverting 1,2-α-l-fucosidase (AfcA) into a highly efficient 1,2-α-l-fucosynthase. The synthase specifically synthesized H type 1-, type 2-, type 3- and type 4-chain-containing oligosaccharides with yields of 57–75% based on acceptor depletion. The synthase was also able to specifically introduce Fuc residues into Lewis a/x antigens to produce Lewis b/y antigens, with yields of 43% and 62%, respectively. In addition, the enzyme efficiently introduced H-antigens into sugar chains of porcine gastric mucins, as revealed by lectin blotting and mass spectroscopy analy...
Source: Glycobiology - November 21, 2016 Category: Biology Authors: Sugiyama, Y., Gotoh, A., Katoh, T., Honda, Y., Yoshida, E., Kurihara, S., Ashida, H., Kumagai, H., Yamamoto, K., Kitaoka, M., Katayama, T. Tags: Glycan Synthesis Source Type: research
Novel aspects of sialoglycan recognition by the Siglec-like domains of streptococcal SRR glycoproteins
Serine-rich repeat glycoproteins are adhesins expressed by commensal and pathogenic Gram-positive bacteria. A subset of these adhesins, expressed by oral streptococci, binds sialylated glycans decorating human salivary mucin MG2/MUC7, and platelet glycoprotein GPIb. Specific sialoglycan targets were previously identified for the ligand-binding regions (BRs) of GspB and Hsa, two serine-rich repeat glycoproteins expressed by Streptococcus gordonii. While GspB selectively binds sialyl-T antigen, Hsa displays broader specificity. Here we examine the binding properties of four additional BRs from Streptococcus sanguinis or Stre...
Source: Glycobiology - November 21, 2016 Category: Biology Authors: Bensing, B. A., Khedri, Z., Deng, L., Yu, H., Prakobphol, A., Fisher, S. J., Chen, X., Iverson, T. M., Varki, A., Sullam, P. M. Tags: Original articles Source Type: research
The structural investigation of glycosaminoglycan binding to CXCL12 displays distinct interaction sites
The stromal cell-derived factor 1α (CXCL12) belongs to the CXC chemokine family and plays an important role in tissue regeneration and the recruitment of stem cells. Here, a stable chemotactic gradient is essential that is formed by the interaction of CXCL12 with the extracellular matrix. Binding properties of CXCL12 to naturally occurring glycosaminoglycans (GAGs) as well as to the artificial highly sulfated hyaluronic acid (HA) are investigated by using a combination of NMR spectroscopy, molecular modeling and molecular dynamics simulations. Our results demonstrate a preferred protein binding for the sulfated GAGs ...
Source: Glycobiology - November 21, 2016 Category: Biology Authors: Panitz, N., Theisgen, S., Samsonov, S. A., Gehrcke, J.-P., Baumann, L., Bellmann-Sickert, K., Köhling, S., Pisabarro, M. T., Rademann, J., Huster, D., Beck-Sickinger, A. G. Tags: Glycan Recognition Source Type: research
Dissecting PUGNAc-mediated inhibition of the pro-survival action of insulin
Previous studies utilizing PUGNAc, the most widely used β-N-acetylglucosaminidase (OGA) inhibitor to increase global O-N-acetylglucosamine (GlcNAc) levels, have reported a variety of effects including insulin resistance as a direct result of elevated O-GlcNAc levels. The notion of OGA inhibition causing insulin resistance was not replicated in studies in which elevated global O-GlcNAc levels were achieved using two other OGA inhibitors. Related to insulin action, work by others has suggested that O-GlcNAc elevation may inhibit the anti-apoptotic action of insulin. Thus, we examined the pro-survival action of insulin u...
Source: Glycobiology - November 21, 2016 Category: Biology Authors: Teo, C. F., El-Karim, E. G., Wells, L. Tags: Original articles Source Type: research
Chitosan conjugation enables intracellular bacteria susceptible to aminoglycoside antibiotic
Most chronic infections are difficult to eradicate because bacteria capable of surviving in host-infected cells may be protected from the killing actions of antibiotics, leading to therapy failures and disease relapses. Here we demonstrated that covalent-coupling chitosan to streptomycin significantly improved intracellular bactericidal capacity towards multiple organisms within phagocytic or nonphagocytic cells. Structure–activity relationship investigations indicated that antibiotic contents, molecular size and positive charges of the conjugate were the key to retain this intracellular bactericidal activity. Mechan...
Source: Glycobiology - November 21, 2016 Category: Biology Authors: Mu, H., Niu, H., Wang, D., Sun, F., Sun, Y., Duan, J. Tags: Chemical Biology Source Type: research
Core-fucosylation plays a pivotal role in hepatitis B pseudo virus infection: a possible implication for HBV glycotherapy
The functions of cell surface proteins, such as growth factor receptors and virus/bacteria-entry receptors, can be dynamically regulated by oligosaccharide modifications. In the present study, we investigated the involvement of glycosylation in hepatitis B virus (HBV) entry into hepatoma cells. Infection of oligosaccharide-remodeling hepatoma cells with a pseudo virus of HBV, bio-nanocapsule (BNC), was evaluated by flow cytometry and confocal microscopy. Among various experiments using several hepatoma cells, marked difference was observed between Huh6 cells and HB611 cells, which were established by HBV gene transfection ...
Source: Glycobiology - November 21, 2016 Category: Biology Authors: Takamatsu, S., Shimomura, M., Kamada, Y., Maeda, H., Sobajima, T., Hikita, H., Iijima, M., Okamoto, Y., Misaki, R., Fujiyama, K., Nagamori, S., Kanai, Y., Takehara, T., Ueda, K., Kuroda, S., Miyoshi, E. Tags: Cell Biology Source Type: research
Inhibition of hyaluronic acid formation sensitizes chronic myelogenous leukemia to treatment with doxorubicin
In the current study we examined the ability of 4-methylumbelliferone (4-MU), which can inhibit hyaluronic acid synthesis, to sensitize K562 chronic myelogenous leukemia (CML) cells to doxorubicin therapy. Exposure of K562 cells to doxorubicin led to increased hyaluronic acid synthase (HAS) gene expression and increased levels of cell surface hyaluronic acid. Furthermore, exposure of K562 cells to exogenous HA caused resistance to doxorubicin-induced cell death. The combination of low dose 4-MU and doxorubicin led to increased apoptosis when compared to higher doses of any agent alone. Additionally, treatment with 4-MU led...
Source: Glycobiology - November 21, 2016 Category: Biology Authors: Uchakina, O. N., Ban, H., Hostetler, B. J., McKallip, R. J. Tags: Cancer Biology Source Type: research
