Genetic variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfate diversity. DOI Creative Commons
Mohand Ouidir Ouidja, Denis Biard, Minh Bao Huynh

et al.

Essays in Biochemistry, Journal Year: 2024, Volume and Issue: 68(4), P. 555 - 578

Published: Dec. 4, 2024

Heparan sulfate (HS) and chondroitin (CS) proteoglycans (PG) consist of a core protein to which the glycosaminoglycan (GAG) chains, HS or CS, are attached through common linker tetrasaccharide. In extracellular space, they involved in regulation cell communication, assuring development homeostasis. The HSPG biosynthetic pathway has documented 51 genes, with many diseases associated defects some them. phenotypic consequences this genetic variation humans, ablation mice, their expression patterns, led phenotypically centered model. model, sequences produced by ubiquitous NDST1, HS2ST HS6ST enzymes essential for normal homeostasis, whereas tissue restricted non-ubiquitous NDST2-4, HS6ST2-3, HS3ST1-6 adaptative behaviors, cognition, responsiveness stimuli, vulnerability disease. model indicates that flux HSPG/CSPG pathways its diverse branches is regulated substrate preferences protein-protein-interactions. This results privileged biosynthesis over CSPGs, explaining phenotypes linkeropathies, disease caused genes tetrasaccharide linker. Documented feedback loops whereby cells regulate sulfation, hence interactions partners, may be similarly implemented, e.g., tyrosine sulfation other posttranslational modifications pathway. Together, HS, specialized can facilitate research better understanding roles physiology pathology.

Language: Английский

Effects of the sulfated polysaccharides dextran sulfate and heparin on shrimp immunity and infection by white spot syndrome virus and Vibrio parahaemolyticus DOI

Soraat Amphan,

Pasunee Laohawutthichai,

Thapanan Jatuyosporn

et al.

Aquaculture Reports, Journal Year: 2025, Volume and Issue: 42, P. 102735 - 102735

Published: March 11, 2025

Language: Английский

Citations

0
Synthetic heparan sulfate mimics based on chitosan derivatives show broad-spectrum antiviral activity DOI Creative Commons
Julia Revuelta, Luciana Rusu, Clara Francés‐Gómez

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 4, 2025

Enveloped viruses enter cells by binding to receptors present on host cell membranes, which trigger internalization and membrane fusion. For many viruses, this either directly or indirectly involves interaction with membrane-anchored carbohydrates, such as heparan sulfate, providing a potential target for broad-spectrum antiviral approach. Based hypothesis, we screened library of functionalized chitosan sulfates that mimic sulfate in cellular membranes inhibition SARS-CoV-2 respiratory syncytial virus (RSV) entry. An array compounds blocking RSV were identified, the lead compound displaying activity against multiple viral strains clinical isolates. Mechanism action studies showed drug block entry irreversibly, likely via virucidal mechanism. Importantly, was non-toxic vivo potent post-exposure therapeutic both RSV. Together, these results highlight carbohydrates antivirals targeting viruses.

Language: Английский

Citations

0
Sulfation pathways in the maintenance of functional beta-cell mass and implications for diabetes DOI Creative Commons
Jonathan Wolf Mueller, Patricia Thomas, Louise T. Dalgaard

et al.

Essays in Biochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Abstract Diabetes Type 1 and 2 are widely occurring diseases. In spite of a vast amount biomedical literature about diabetic processes in general, links to certain biological only becoming evident these days. One such area biology is the sulfation small molecules, as steroid hormones or metabolites from gastrointestinal tract, well larger biomolecules, proteins proteoglycans. Thus, modulating physicochemical propensities different sulfate acceptors, resulting enhanced solubility, expedited circulatory transit, macromolecular interaction. This review lists evidence for involvement pathways maintenance functional pancreatic beta-cell mass implications diabetes, grouped into various classes sulfated biomolecule. Complex heparan sulfates might play role development beta-cells. The sulfolipids sulfatide sulfo-cholesterol contribute health. beta-cells, there very few with confirmed on some tyrosine residues, IRS4 molecule being one them. Sulfated hormones, estradiol-sulfate vitamin-D-sulfate, may facilitate downstream signaling following de-sulfation. Indoxyl metabolite intestine, that causes kidney damage, contributing disease. Finally, technological perspective, sulfate, heparin, chondroitin all be involved next-generation transplantation. Sulfation beta-cells through multiple mechanisms. A more coherent understanding diabetes will discussion guide future research.

Language: Английский

Citations

1
In silico approaches for better understanding cysteine cathepsin-glycosaminoglycan interactions DOI Creative Commons

Krzysztof K. Bojarski,

Alexis David, Fabien Lecaille

et al.

Carbohydrate Research, Journal Year: 2024, Volume and Issue: 543, P. 109201 - 109201

Published: July 6, 2024

Cysteine cathepsins constitute the largest cathepsin family, with 11 proteases in human that are present primarily within acidic endosomal and lysosomal compartments. They involved turnover of intracellular extracellular proteins. synthesized as inactive procathepsins converted to mature active forms. Cathepsins play important roles physiological pathological processes and, therefore, receive increasing attention potential therapeutic targets. Their maturation activity can be regulated by glycosaminoglycans (GAGs), long linear negatively charged polysaccharides composed recurring dimeric units. In this review, we summarize recent computational progress field (pro)cathepsin-GAG complexes analyses.

Language: Английский

Citations

0
Glycosaminoglycan Concentration and Sulfation Patterns of Biohybrid Polymer Matrices Direct Microvascular Network Formation and Stability DOI Creative Commons
Yanuar Dwi Putra Limasale, Maximilian Fusenig,

Marten Samulowitz

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 10, 2024

Abstract Complexation with sulfated glycosaminoglycans (GAGs) regulates the signaling of pro‐angiogenic growth factors in vivo. To use this principle modulating microvascular network formation and stability vitro, a library biohybrid hydrogels containing heparin, highly GAG, or its selectively desulfated derivatives, is prepared. The are applied to systematically investigate effects GAG concentration sulfation patterns on embedded cultures human umbilical vein endothelial cells (HUVECs) cocultures HUVECs mesenchymal stromal (MSCs). Formation morphology networks, cell expansion, extracellular matrix (ECM) protein deposition found be significantly influenced by hydrogel's concentrations patterns, presumably through differences resulting availability bioactivity GAG‐binding factors. In particular, either low heparin (500 µ m ) higher at 6O N position resulted dense, stable networks. respective conditions also displayed enhanced proliferation ECM deposition, leading increased stiffness. Therefore, precisely tuning affinity materials for effectively enhances vascularization engineered tissue constructs vitro.

Language: Английский

Citations

0
Sulfation pathways in times of change DOI Creative Commons
Jonathan Wolf Mueller, Daniela Fietz, Irundika H.K. Dias

et al.

Essays in Biochemistry, Journal Year: 2024, Volume and Issue: 68(4), P. 379 - 382

Published: Dec. 1, 2024

Abstract Sulfation pathways are an essential part of overall sulfur metabolism. mainly about sulfate activation, and the making breaking biological esters. This special issue features some extended reflection on what was presented at SUPA 2023 meeting Pathways. Novel insights into synthesis analytics sulfate, sulfated conjugates, protein persulfides presented. Oxysterol sulfates as emerging sulfo-metabolites. enzymes discussed in various disease settings. also presents polysaccharide sulfotransferases their functional characterization. Finally, cytoplasmic highlighted with regards to impact DNA-modification, context endocrine disruptors. All all, thought-provoking findings, potential guide stimulate future research field sulfation beyond.

Language: Английский

Citations

0
Genetic variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfate diversity. DOI Creative Commons
Mohand Ouidir Ouidja, Denis Biard, Minh Bao Huynh

et al.

Essays in Biochemistry, Journal Year: 2024, Volume and Issue: 68(4), P. 555 - 578

Published: Dec. 4, 2024

Heparan sulfate (HS) and chondroitin (CS) proteoglycans (PG) consist of a core protein to which the glycosaminoglycan (GAG) chains, HS or CS, are attached through common linker tetrasaccharide. In extracellular space, they involved in regulation cell communication, assuring development homeostasis. The HSPG biosynthetic pathway has documented 51 genes, with many diseases associated defects some them. phenotypic consequences this genetic variation humans, ablation mice, their expression patterns, led phenotypically centered model. model, sequences produced by ubiquitous NDST1, HS2ST HS6ST enzymes essential for normal homeostasis, whereas tissue restricted non-ubiquitous NDST2-4, HS6ST2-3, HS3ST1-6 adaptative behaviors, cognition, responsiveness stimuli, vulnerability disease. model indicates that flux HSPG/CSPG pathways its diverse branches is regulated substrate preferences protein-protein-interactions. This results privileged biosynthesis over CSPGs, explaining phenotypes linkeropathies, disease caused genes tetrasaccharide linker. Documented feedback loops whereby cells regulate sulfation, hence interactions partners, may be similarly implemented, e.g., tyrosine sulfation other posttranslational modifications pathway. Together, HS, specialized can facilitate research better understanding roles physiology pathology.

Language: Английский

Citations

0