Article
Clinical Neurology
Natalia Perez-Lopez, Carla Martin, Beatriz Garcia, Maria Pilar Solis-Hernandez, David Rodriguez, Ignacio Alcalde, Jesus Merayo, Ivan Fernandez-Vega, Luis M. Quiros
Summary: The saccharide chains of heparan sulfate play a crucial role in the pathogenesis of Alzheimer's disease, with differential transcription of biosynthetic genes observed in different brain regions and stages of AD pathology. The study revealed more alterations in gene transcription in moderate AD patients compared to mild cases, with fewer changes in genes related to early stages of synthesis in severe patients and an overexpression of late-stage genes. These alterations correlated with progressive brain atrophy, particularly in the cerebellum, and were consistent with immunohistochemical detection of certain heparan sulfate epitopes.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Vaishali N. Patel, Dallas L. Pineda, Elsa Berenstein, Belinda R. Hauser, Sophie Choi, Michaela Prochazkova, Changyu Zheng, Corinne M. Goldsmith, Toin H. van Kuppevelt, Ashok Kulkarni, Yuefan Song, Robert J. Linhardt, Alejandro M. Chibly, Matthew P. Hoffman
Summary: Heparan sulfate 3-O-sulfotransferases generate highly sulfated rare heparan sulfate epitopes, and their knockout affects epithelial morphogenesis and salivary gland function.
Article
Chemistry, Physical
Rylee Wander, Andrea M. Kaminski, Zhangjie Wang, Eduardo Stancanelli, Yongmei Xu, Vijayakanth Pagadala, Jine Li, Juno M. Krahn, Truong Quang Pham, Jian Liu, Lars C. Pedersen
Summary: The study presents the crystal structures of 3-OST-5 with substrates and PAP, revealing its substrate specificity and anti-factor Xa activity. The enzyme prefers to sulfate a 6-O-sulfo glucosamine saccharide that is surrounded by glucuronic acid. Additionally, it was found that substrate specificity is not only determined by the side chains of amino acid residues in the active site, but also by the conformational flexibility of 2-O-sulfated iduronic acid in the saccharide substrates.
Article
Chemistry, Applied
Tianji Zhang, Mingjia Yu, Honglian Li, Marco Maccarana, Wei Zhang, Deling Shi, Ying Kan, Xiao Zhang, Lianli Chi, Ulf Lindahl, Hongmei Li, Jin-ping Li, Tianwei Tan
Summary: This study investigated the functional interactions between glucuronyl 5-epimerase (Hsepi) and hexuronyl 2-O-sulfotransferase (Hs2st) and glucosaminyl 6-O-sulfotransferase (Hs6st) using an isotope exchange approach. The results showed that the binding of these enzymes plays an important role in the efficiency of substrate conversion. Furthermore, experimental evidence suggested the formation of a functional complex between Hsepi and Hs6st in cells, and the inability to achieve simultaneous 2-O and 6-O sulfation in vitro.
CARBOHYDRATE POLYMERS
(2023)
Article
Multidisciplinary Sciences
Casper de Boer, Zachary Armstrong, Vincent A. J. Lit, Uri Barash, Gijs Ruijgrok, Ilanit Boyango, Merle M. Weitzenberg, Sybrin P. Schroder, Alexi J. C. Sarris, Nico J. Meeuwenoord, Pedro Bule, Yasmine Kayal, Neta Ilan, Jeroen D. C. Codee, Israel Vlodavsky, Herman S. Overkleeft, Gideon J. Davies, Liang Wu
Summary: Research has shown that by developing effective HPSE inhibitors, extracellular HPSE activity can be reduced, thereby reducing the aggressiveness of cancer and potentially controlling pathological HPSE-driven malignancies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Chunli Kong, Martin Beukema, Min Wang, Bart J. de Haan, Paul de Vos
Summary: 2'-FL and pectins can inhibit pathogen adhesion to gut epithelial cells by modifying cell membrane glycosylation and inflammatory genes. Pectins can reduce the adhesion of certain pathogens by altering glycosylation genes. K. pneumoniae LMG20218 downregulates inflammatory genes, which can be restored by pectin treatment.
Article
Chemistry, Medicinal
Shuang Qu, Xiaoli Huang, Xiaoling Guo, Zhihai Zheng, Tiannan Wei, Biyun Chen
Summary: Through comparative RNA-seq analysis, we identified differential expression of EMT genes in AML patients and constructed a metastasis-related EMT signature (MEMTs). Analysis on different cohorts showed that MEMTs were associated with prognosis and chemotherapy response in AML. Functional experiments demonstrated that CDH2 is a key gene promoting leukemia cell metastasis among the three MEMTs genes. These findings provide potential predictive factors for AML prognosis and chemotherapy response, with CDH2 as a potential therapeutic target.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2023)
Review
Biochemistry & Molecular Biology
Heidi N. du Preez, Colleen Aldous, Melvin R. Hayden, Hendrik G. Kruger, Johnson Lin
Summary: The glycocalyx, a mesh of proteins and carbohydrates, plays an important role in protecting cells. The degree of sulfation and the position of sulfate groups on the glycocalyx determine its function. Highly sulfated glycocalyx can repel SARS-CoV-2, but undersulfation may facilitate viral entry. Sulfation also affects immune modulation, inflammation, vascular function, and protection against stress. Sulfation depends on the availability of inorganic sulfate, which can be influenced by genetic and environmental factors.
Article
Biochemistry & Molecular Biology
Hao Cui, Zhaoguang Wang, Tianji Zhang, Jin-ping Li, Jianping Fang
Summary: The translation explores the role of Heparan sulfate (HS) in protein recognition and interaction, highlighting the importance of specific sulfation and epimerization patterns modulated by Golgi-localized enzymes. The study investigates the effects of restoring Hsepi in mutant MEF cells, showing increased IdoA residues and rescued cell signaling, although Hsepi knockout did not influence cellular transport or enzymatic activity of 2OST. These findings suggest potential differences in regulatory mechanisms for 2OST and Hsepi.
Article
Peripheral Vascular Disease
Olga Berillo, Sofiane Ouerd, Noureddine Idris-Khodja, Asia Rehman, Chantal Richer, Daniel Sinnett, Anne E. Kwitek, Pierre Paradis, Ernesto L. Schiffrin
Summary: Chromosome 2 introgression from normotensive Brown Norway rats reduced blood pressure and vascular inflammation in hypertensive Dahl salt-sensitive rats, with two differentially expressed genes identified: Enpep associated with reduced vascular inflammation under NSD, and Hs2st1 associated with increased vascular inflammation under HSD.
Article
Cell Biology
Rana El Masri, Amal Seffouh, Caroline Roelants, Ilham Seffouh, Evelyne Gout, Julien Perard, Fabien Dalonneau, Kazuchika Nishitsuji, Fredrik Noborn, Mahnaz Nikpour, Goran Larson, Yoann Cretinon, Melanie Friedel-Arboleas, Kenji Uchimura, Regis Daniel, Hugues Lortat-Jacob, Odile Filhol, Romain R. Vives
Summary: This study found that human HSulf-2 enzyme carries a chondroitin/dermatan sulfate glycosaminoglycan (GAG) chain, which regulates the enzyme's activity and is promoted by mammalian hyaluronidase.
Article
Microbiology
Bradley E. Hiller, Yongjun Yin, Yi-Chieh Perng, Italo de Araujo Castro, Lindsey E. Fox, Marissa C. Locke, Kristen J. Monte, Carolina B. Lopez, David M. Ornitz, Deborah J. Lenschow
Summary: This study identifies a novel antiviral and inflammatory role for FGFs in the lung airway epithelium and confirms that early and robust IAV infection of alveolar cells results in more severe disease.
Article
Biochemistry & Molecular Biology
Lingbo Sun, Andriana Konstantinidi, Zilu Ye, Rebecca Nason, Yuecheng Zhang, Christian Bull, Barbro Kahl-Knutson, Lars Hansen, Hakon Leffler, Sergey Y. Vakhrushev, Zhang Yang, Henrik Clausen, Yoshiki Narimatsu
Summary: Researchers engineered sulfotransferase genes in HEK293 cells to achieve sulfation modification of O-glycans. They used this engineered cell library to study the binding specificity between galectin-4 and sulfated O-glycans.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Genetics & Heredity
Melissa Cizeron, Laure Granger, Hannes E. Bulow, Jean-Louis Bessereau
Summary: The study systematically mutated genes encoding HS modification enzymes in Caenorhabditis elegans to analyze their impact on excitatory and inhibitory neuromuscular junctions. It was found that specific modifications of glycosaminoglycan chains may contribute to a sugar code involved in synapse specificity. Additionally, the study showed that 3-O-sulfation of SDN-1 is required for maintaining proper levels of the extracellular matrix protein MADD-4/Punctin, which defines the identity of excitatory and inhibitory synaptic domains.
Article
Nanoscience & Nanotechnology
Dingze Mang, Sona Rani Roy, Qizheng Zhang, Xunwu Hu, Ye Zhang
Summary: This study developed HS-instructed self-assembling peptides to inhibit cancer cell migration by hindering the binding of HSPG with HBEGF, leading to the suppression of FAK and ERK activation. This approach shows promise as a synthetic therapeutic strategy for targeted cancer migration inhibition.
ACS APPLIED MATERIALS & INTERFACES
(2021)
