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Junko Nio-Kobayashi, Hazirah B Z Abidin, Jeremy K Brown, Toshihiko Iwanaga, Andrew W Horne, W Colin Duncan
Sialylation creates a negative charge on the cell surface that can interfere with blastocyst implantation. For example, α2,6-sialylation on terminal galactose, catalyzed by the sialyltransferase ST6GAL1, inhibits the binding of galectin-1, a β-galactoside-binding lectin. We recently reported the potential involvement of galectin-1 and -3 in the pathogenesis of tubal ectopic pregnancy; however, the precise role of galectins and their ligand glycoconjugates remain unclear. Here, we investigated the expression of the genes encoding α2,3- and α2,6-galactoside sialyltransferases (ST3GAL1 - 6 and ST6GAL1 - 2) and the localization of sialic acids in the Fallopian tube of women with or without ectopic implantation...
October 5, 2016: Molecular Reproduction and Development
Pablo H H Lopez, Susan Aja, Kazuhiro Aoki, Marcus M Seldin, Xia Lei, Gabriele V Ronnett, G William Wong, Ronald L Schnaar
Sialyltransferases are a family of 20 gene products in mice and humans that transfer sialic acid from its activated precursor, CMP-sialic acid, to the terminus of glycoprotein and glycolipid acceptors. ST3Gal-II (coded by the St3gal2 gene) transfers sialic acid preferentially to the 3-position of galactose on the Galβ1-3GalNAc terminus of gangliosides GM1 and GD1b to synthesize GD1a and GT1b respectively. Mice with a targeted disruption of St3gal2 unexpectedly displayed late-onset obesity and insulin resistance...
September 28, 2016: Glycobiology
Rémi Szabo, Danielle Skropeta
Hypersialylation of tumor cell surface proteins along with a marked upregulation of sialyltransferase (ST) activity is a well-established hallmark of cancer. Due to the critical role of STs in tumor growth and progression, ST inhibition has emerged as a potential new antimetastatic strategy for a range of cancers including pancreatic and ovarian. Human STs are divided into subtypes based on their linkage and acceptor molecule, with each subtype controlling the synthesis of specific sialylated structures with unique biological roles...
September 28, 2016: Medicinal Research Reviews
Yojiro Hamada, Yusuke Kanematsu, Masanori Tachikawa
The sialyltransferase is an enzyme that transfers the sialic acid moiety from cytidine 5'-monophospho-N-acetyl-neuraminic acid (CMP-NeuAc) to the terminal position of glycans. To elucidate the catalytic mechanism of sialyltransferase, we explored the potential energy surface along the sialic acid transfer reaction coordinates by the hybrid quantum mechanics/molecular mechanics method on the basis of the crystal structure of sialyltransferase CstII. Our calculation demonstrated that CstII employed an SN1-like reaction mechanism via the formation of a short-lived oxocarbenium ion intermediate...
October 11, 2016: Biochemistry
Joaquina X Mascarenhas, Nikolay Korokhov, Lisa Burger, Ademola Kassim, Jason Tuter, Daniel Miller, Trissa Borgschulte, Henry J George, Audrey Chang, David J Pintel, David Onions, Kevin J Kayser
Contamination by the parvovirus minute virus of mice (MVM) remains a challenge in Chinese hamster ovary (CHO) biopharmaceutical production processes. Although infrequent, infection of a bioreactor can be catastrophic for a manufacturer, can impact patient drug supply and safety, and can have regulatory implications. We evaluated engineering a CHO parental cell line (CHOZN(®) GS(-/-) ) to create a new host cell line that is resistant to MVM infection by modifying the major receptors used by the virus to enter cells...
September 19, 2016: Biotechnology and Bioengineering
Werner Crous, Kevin J Naidoo
Mammalian sialyltransferases play a role in the metastasis of various cancers in humans. Inhibitors of these enzymes will in principle be able to directly inhibit aberrant sialylation in cancer. Inhibitors of ST3Gal-I resembling the donor component of SN1 Transition State structures were previously evaluated as part of a kinetics study. Here, using classical dynamics simulations and free energy perturbation calculations, we rationalize the performance of three of these donor analogue ST3Gal-I enzyme inhibitors...
October 15, 2016: Bioorganic & Medicinal Chemistry
Kazuki Miyaji, Jun-Ichi Furukawa, Youichi Suzuki, Naoki Yamamoto, Yasuro Shinohara, Nobuhiro Yuki
There is a case report of a patient with overlapping Guillain-Barré syndrome and Bickerstaff brainstem encephalitis after infection with herpes simplex virus type 1 (HSV-1), who carried high titers of serum anti-GQ1b IgG antibodies. Several studies have linked viral infection to the modulation of ganglioside expression such as human T-lymphotropic virus to GD2 and simian virus 40 to GM3. Also, enhancement of the expression of GM2 on the cell membrane after cytomegalovirus infection has been reported. The objective of this study was to unveil the relationship between HSV-1 infection and the alteration of cellular ganglioside expression in neuronal and glial cell lines...
August 18, 2016: Carbohydrate Research
Anwen Wei, Bo Fan, Yujie Zhao, Han Zhang, Liping Wang, Xiao Yu, Qingmin Yuan, Deyong Yang, Shujing Wang
ST6Gal-I sialyltransferase adds α2,6-linked sialic acids to the terminal ends of glycan chains of glycoproteins and glycolipids. ST6Gal-I is reportedly upregulated in many cancers, including hepatocellular carcinoma, ovarian cancer and breast cancer. However, the expression and function of ST6Gal-I in prostate cancer (PCa) and the mechanism underlying this function remain largely unknown. In this study, we observed that ST6Gal-I expression was upregulated in human PCa tissues compared to non-malignant prostate tissues...
August 30, 2016: Oncotarget
Jaewoo Song, Cheng Xue, John S Preisser, Drake W Cramer, Katie L Houck, Guo Liu, Aaron R Folsom, David Couper, Fuli Yu, Jing-Fei Dong
VWF is extensively glycosylated with biantennary core fucosylated glycans. Most N-linked and O-linked glycans on VWF are sialylated. FVIII is also glycosylated, with a glycan structure similar to that of VWF. ST3GAL sialyltransferases catalyze the transfer of sialic acids in the α2,3 linkage to termini of N- and O-glycans. This sialic acid modification is critical for VWF synthesis and activity. We analyzed genetic and phenotypic data from the Atherosclerosis Risk in Communities (ARIC) study for the association of single nucleotide polymorphisms (SNPs) in the ST3GAL4 gene with plasma VWF levels and FVIII activity in 12,117 subjects...
2016: PloS One
Yu Ri Jung, Jung-Jin Park, Yeung Bae Jin, Yuan Jie Cao, Myung-Jin Park, Eun Ju Kim, Minyoung Lee
Aberrant sialylation has long been correlated with human cancer. Increased ST6 Gal I (β-galactoside α 2, 6 sialyltransferase) and consequently higher levels of cell-surface α 2, 6 sialylation has been associated with human colorectal cancer (CRC) metastasis. We have extensive circumstantial data that sialylation is connected to cancer metastasis, but we do not understand in detail how sialylation can switch on/off multiple steps in cancer metastasis. To investigate the molecular mechanism underlying the ST6Gal I-mediated metastasis of CRC, we silenced the ST6Gal I gene in a metastatic SW620 CRC cell line (SW620-shST6Gal I) and examined the metastatic behavior of the cells...
August 24, 2016: Carcinogenesis
Pierre-André Gilormini, Cédric Lion, Maxence Noel, Marie-Ange Krzewinski-Recchi, Anne Harduin-Lepers, Yann Guérardel, Christophe Biot
Natural and synthetically modified CMP-activated sialic acids are essential research tools in the field of glycobiology: among other applications, they can be used to probe glycans, detect sialylation defects at the cell surface, or carry out detailed studies of sialyltransferase activities. However, these chemical tools are notoriously unstable because of hydrolytic decomposition, and are very time-consuming and costly to obtain. They are nigh impossible to store with satisfactory purity, and their preparation requires multiple laborious purification steps that usually lead to heavy product loss...
August 19, 2016: Glycobiology
Qi Bai, Li Liu, Wei Xi, Jiajun Wang, Yu Xia, Yang Qu, Ying Xiong, Qilai Long, Jiejie Xu, Jianming Guo
BACKGROUND: Sialyltransferase ST6GalNAc-1 is highly expressed in tumor cells and associated with tumor aggressiveness and poor prognosis. In the present study, we aimed to investigate the clinical and prognostic significance of sialyltransferase ST6GalNAc-1 in patients with non-metastatic ccRCC. RESULTS: High expression of ST6GalNAc-1 in tumor tissue was an independent prognostic factor for overall survival (p<0.001) and recurrence free survival (p<0.001) in multivariate analysis...
August 12, 2016: Oncotarget
Aurore Drolez, Elodie Vandenhaute, Clément Philippe Delannoy, Justine Hélène Dewald, Fabien Gosselet, Romeo Cecchelli, Sylvain Julien, Marie-Pierre Dehouck, Philippe Delannoy, Caroline Mysiorek
The ST6GALNAC5 gene that encodes an α2,6-sialyltransferase involved in the biosynthesis of α-series gangliosides, was previously identified as one of the genes that mediate breast cancer metastasis to the brain. We have shown that the expression of ST6GALNAC5 in MDA-MB-231 breast cancer cells resulted in the expression of GD1α ganglioside at the cell surface. By using a human blood-brain barrier in vitro model recently developed, consisting in CD34⁺ derived endothelial cells co-cultivated with pericytes, we show that ST6GALNAC5 expression decreased the interactions between the breast cancer cells and the human blood-brain barrier...
2016: International Journal of Molecular Sciences
Almut H Vollmer, Makda S Gebre, Dale L Barnard
Assessment of influenza virus disease progression and efficacy of antiviral therapy in the widely used mouse models relies mostly on body weight loss and lung virus titers as markers of disease. However, both parameters have their shortcomings. Therefore, the aim of our study was to find non-invasive markers in the murine model of severe influenza that could detect disease early and predict disease outcome. BALB/c mice were lethally infected with influenza A(H1N1)pdm09 virus and serum samples were collected at various time points...
September 2016: Antiviral Research
Roxana E Teppa, Daniel Petit, Olga Plechakova, Virginie Cogez, Anne Harduin-Lepers
Cell surface of eukaryotic cells is covered with a wide variety of sialylated molecules involved in diverse biological processes and taking part in cell-cell interactions. Although the physiological relevance of these sialylated glycoconjugates in vertebrates begins to be deciphered, the origin and evolution of the genetic machinery implicated in their biosynthetic pathway are poorly understood. Among the variety of actors involved in the sialylation machinery, sialyltransferases are key enzymes for the biosynthesis of sialylated molecules...
2016: International Journal of Molecular Sciences
Wei Deng, Andrew R Ednie, Jianyong Qi, Eric S Bennett
Dilated cardiomyopathy (DCM), the third most common cause of heart failure, is often associated with arrhythmias and sudden cardiac death if not controlled. The majority of DCM is of unknown etiology. Protein sialylation is altered in human DCM, with responsible mechanisms not yet described. Here we sought to investigate the impact of clinically relevant changes in sialylation on cardiac function using a novel model for altered glycoprotein sialylation that leads to DCM and to chronic stress-induced heart failure (HF), deletion of the sialyltransferase, ST3Gal4...
September 2016: Basic Research in Cardiology
Hyun-Kyoung Yoon, Hyun-Kyu An, Min Jung Ko, Kyoung-Sook Kim, Seo-Won Mun, Dong-Hyun Kim, Cheol Min Kim, Cheorl-Ho Kim, Young Whan Choi, Young-Choon Lee
In this research, we firstly demonstrated that physcion, an anthraquinone derivative, specifically increased the expression of the human α2,8-sialyltransferase (hST8Sia VI) gene in SK-N-BE(2)-C human neuroblastoma cells. To establish the mechanism responsible for the up-regulation of hST8Sia VI gene expression in physcion-treated SK-N-BE(2)-C cells, the putative promoter region of the hST8Sia VI gene was functionally characterized. Promoter analysis with serially truncated fragments of the 5'-flanking region showed that the region between -320 and -240 is crucial for physcion-induced transcription of hST8Sia VI in SK-N-BE(2)-C cells...
2016: International Journal of Molecular Sciences
Roberta Salinas-Marín, Rosella Mollicone, Iván Martínez-Duncker
The human Golgi Cytidine-5'-monophospho-N-acetylneuraminic acid (CMP-Sia) transporter SLC35A1, a member of the nucleotide sugar transporter family, translocates CMP-Sia from the cytosol into the Golgi lumen where sialyltransferases use it as donor substrate for the synthesis of sialoglycoconjugates. In 2005, we reported a novel Congenital Disorder of Glycosylation (CDG) termed CDG-IIf or SLC35A1-CDG, characterized by macrothrombocytopenia, neutropenia and complete lack of the sialyl-Le(x) antigen (NeuAcα2-3Galβ1-4(Fucα1-3)GlcNAc-R) on polymorphonuclear cells...
July 7, 2016: Glycoconjugate Journal
Clément P Delannoy, Yoann Rombouts, Sophie Groux-Degroote, Stephanie Holst, Bernadette Coddeville, Anne Harduin-Lepers, Manfred Wuhrer, Elisabeth Elass-Rochard, Yann Guerardel
The human acute monocytic leukemia cell line THP-1 is widely used as an in vitro phagocytic cell model, since it exhibits several immune properties similar to native monocyte-derived macrophages. In this study, we investigated the alteration of N- and O- linked glycans as well as glycosphingolipids, during THP-1 differentiation, combining mass spectrometry, flow cytometry and quantitative real-time PCR. Mass spectrometry revealed that macrophage differentiation led to a marked upregulation of expression of GM3 ganglioside as well as an increase of complex-type structures, particularly tri-antennary glycans, occurring at the expense of high-mannose N-glycans...
June 28, 2016: Journal of Proteome Research
Xixi Chen, Liping Wang, Yujie Zhao, Shiqi Yuan, Qiang Wu, Xiaoling Zhu, Bachir Niang, Shujing Wang, Jianing Zhang
The β-galactoside α2-6-sialyltransferase 1 (ST6Gal-I) is the principal sialyltransferase responsible for the addition of α2-6-sialic acid to the termini N-glycans on cell surface. Although ST6Gal-I in cancer cell resistance to chemotherapeutics agents has been previously reported, the role of ST6Gal-I in clinical drug resistance of hepatocellular carcinoma (HCC) is not fully understood. In this study, we found that knockdown of ST6Gal-I increased the sensitivity of hepatocarcinoma MHCC97-H cells to docetaxel treatment by instigating the process of apoptosis...
June 21, 2016: Oncotarget
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