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Glycosaminoglycans and proteoglycans: interplay between structure and function

Grant number: 15/03964-6
Support type:Research Projects - Thematic Grants
Duration: July 01, 2015 - June 30, 2021
Field of knowledge:Biological Sciences - Biochemistry - Chemistry of Macromolecules
Principal Investigator:Helena Bonciani Nader
Grantee:Helena Bonciani Nader
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Co-Principal Investigators:Ivarne Luis dos Santos Tersariol
Assoc. researchers:Carla Cristina Lopes de Azevedo ; Edgar Julian Paredes-Gamero ; Edwin Alexander Yates ; Fábio Dupart Nascimento ; Giselle Zenker Justo ; João Roberto Maciel Martins ; Juliana Luporini Dreyfuss Regatieri ; Leny Toma ; Maria Aparecida da Silva Pinhal ; Vivien Jane Coulson-Thomas ; Yara Maria Corrêa da Silva Michelacci
Associated grant(s):20/04899-1 - Interaction of SARS-CoV-2 spike protein with heparin: therapeutic potential, AP.R
20/02577-7 - Multi-User Equipment approved in grant 2015/03964-6: column chromatography system AKTA Pure 25 M, AP.EMU
16/02852-2 - Multi-usar equipment approved in grant 2015/03964-6: acquisition of a stopped-flow Cd system, AP.EMU
Associated scholarship(s):18/25911-0 - Role of heparan sulfate proteoglycan in cell malignance, BP.IC
17/05707-6 - Heparan sulfate proteoglycans in cell dynamics, BP.PD
17/06255-1 - Modulation of serine protease HTRA1 activity by heparan sulfate proteoglycans, BP.PD
16/19158-1 - Extraction, purification and structural characterization of glycosaminoglycans, BP.IC

Abstract

The glycoconjugates, including glycosaminoglycans (GAGs), belong to the most abundant class of structurally diverse and heterogeneous molecules present in the extracellular matrix and on the cell surface. Unlike nucleic acids and proteins, the information necessary for their biosynthesis does not have a known code. The diverse and heterogeneous structures are the result of the action of glycosyltransferases, epimerases and sulfotransferases that alter the substitution pattern and stereochemistry of sugar residues at specific sites along each polysaccharide chain. As a result, at the end of biosynthesis, there will be a large number of structurally and functionally distinct functional chemical entities. The GAGs structure-function relationship is an example of a complex biological system where there is redundancy and its plasticity is brought to life via the number of possibilities for only one of its constituent disaccharide units. Several questions remain to be answered regarding the structure of GAGs and therefore their functions and one of the key aspects to this approach is the understanding of their biosynthesis. This project aims to study the role of GAGs in cell biology using different models and approaches whose results are complementary and essential to achieve the objectives: 1) functional complex among cell surface proteoglycans (PGs), integrins, cell receptors and extracellular matrix components; 2) PGs in cellular cargo trafficking; 3) GAG: interaction and modulation of endoproteases and endoglycosidases activity; 4) and GAG fragments: structural features and disaccharide sequence and conformational studies; 5) GAG in cellular transformation. (AU)

Scientific publications (21)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MENEGHETTI, MARIA C. Z.; DEBONI, PAULA; PALOMINO, CARLOS M. V.; BRAGA, LUIZ P.; CAVALHEIRO, RENAN P.; VIANA, GUSTAVO M.; YATES, EDWIN A.; NADER, HELENA B.; LIMA, MARCELO A. ER-Golgi dynamics of HS-modifying enzymes via vesicular trafficking is a critical prerequisite for the delineation of HS biosynthesis. Carbohydrate Polymers, v. 255, MAR 1 2021. Web of Science Citations: 0.
CHIARANTIN, GABRIELLY M. D.; DELGADO-GARCIA, LINA M.; ZAMPRONI, LAURA N.; LIMA, MARCELO A.; NADER, HELENA B.; TERSARIOL, IVARNE L. S.; PORCIONATTO, MARIMELIA. Neuroprotective effect of heparin Trisulfated disaccharide on ischemic stroke. GLYCOCONJUGATE JOURNAL, JAN 2021. Web of Science Citations: 0.
RODRIGUES-JUNIOR, DORIVAL MENDES; DE ANDRADE PELARIN, MARIA FERNANDA; NADER, HELENA BONCIANI; VETTORE, ANDRE LUIZ; SILVA PINHAL, MARIA APARECIDA. MicroRNA-1252-5p Associated with Extracellular Vesicles Enhances Bortezomib Sensitivity in Multiple Myeloma Cells by Targeting Heparanase. ONCOTARGETS AND THERAPY, v. 14, p. 455-467, 2021. Web of Science Citations: 0.
ESTEVES, GABRIELA NOHEMI NUNEZ; FERRAZ, LETICIA SILVA; ALVAREZ, MARCELA MACIEL PALACIO; DA COSTA, CLAUDIA ALVES; LOPES, RAYSSA DE MELLO; TERSARIOL, IVARNE LUIS DOS SANTOS; RODRIGUES, TIAGO. BRAF and NRAS mutated melanoma: Different Ca2+ responses, Na+/Ca2+ exchanger expression, and sensitivity to inhibitors. Cell Calcium, v. 90, SEP 2020. Web of Science Citations: 0.
VIANA, GUSTAVO MONTEIRO; GONZALEZ, ESTEBAN ALBERTO; PALACIO ALVAREZ, MARCELA MACIEL; CAVALHEIRO, RENAN PELLUZZI; DO NASCIMENTO, CINTHIA CASTRO; BALDO, GUILHERME; D'ALMEIDA, VANIA; DE LIMA, MARCELO ANDRADE; PSHEZHETSKY, V, ALEXEY; NADER, HELENA BONCIANI. Cathepsin B-associated Activation of Amyloidogenic Pathway in Murine Mucopolysaccharidosis Type I Brain Cortex. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 4 FEB 2020. Web of Science Citations: 0.
PALHARES, LAIS C. G. F.; BRITO, ADRIANA S.; DE LIMA, MARCELO A.; NADER, HELENA B.; LONDON, JAMES A.; BARSUKOV, IGOR L.; ANDRADE, GIULIANNA P. V.; YATES, EDWIN A.; CHAVANTE, SUELY F. A further unique chondroitin sulfate from the shrimp Litopenaeus vannamei with antithrombin activity that modulates acute inflammation. Carbohydrate Polymers, v. 222, OCT 15 2019. Web of Science Citations: 0.
MENDES, ALINE; MENEGHETTI, MARIA C. Z.; PALLADINO, MARCELLY VALLE; JUSTO, GISELLE ZENKER; SASSAKI, GUILHERME L.; FAREED, JAWED; LIMA, MARCELO A.; NADER, HELENA B. Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants. Molecules, v. 24, n. 16 AUG 2019. Web of Science Citations: 0.
SIMOES, PRISCILA S. R.; ZANELATTO, ALEXIA O.; ASSIS, MIRIAN C.; VARELLA, PEDRO PAULO V.; YACUBIAN, ELZA MARCIA; CARRETE, HENRIQUE; CENTENO, RICARDO; ARAUJO, MARIANA S.; CAVALHEIRO, ESPER A.; TERSARIOL, IVARNE LUIS S.; MOTTAT, GUACYARA; NAFFAH-MAZZACORATTI, MARIA DA GRACA. Plasma kallikrein-kinin system contributes to peripheral inflammation in temporal lobe epilepsy. Journal of Neurochemistry, v. 150, n. 3, p. 296-311, AUG 2019. Web of Science Citations: 1.
SOUSA ONYEISI, JESSICA OYIE; DE ALMEIDA PERNAMBUCO FILHO, PAULO CASTANHO; LOPES, SILVANA DEARAUJO; NADER, HELENA BONCIANI; LOPES, CARLA CRISTINA. Heparan sulfate proteoglycans as trastuzumab targets in anoikis-resistant endothelial cells. Journal of Cellular Biochemistry, v. 120, n. 8, p. 13826-13840, AUG 2019. Web of Science Citations: 0.
SIMOES, PRISCILA S. R.; ZANELATTO, ALEXIA O.; ASSIS, MIRIAN C.; VARELLA, PEDRO PAULO V.; YACUBIAN, ELZA MARCIA; CARRETE, HENRIQUE; CENTENO, RICARDO; ARAUJO, MARIANA S.; CAVALHEIRO, ESPER A.; TERSARIOL, IVARNE LUIS S.; MOTTA, GUACYARA; NAFFAH-MAZZACORATTI, MARIA DA GRACA. Plasma kallikrein-kinin system contributes to peripheral inflammation in temporal lobe epilepsy. Journal of Neurochemistry, JULY 2019. Web of Science Citations: 0.
RODRIGUES, TIAGO; NUNEZ ESTEVEZ, GABRIELA NOHEMI; DOS SANTOS TERSARIOL, IVARNE LUIS. Na+/Ca2+ exchangers: Unexploited opportunities for cancer therapy?. Biochemical Pharmacology, v. 163, p. 357-361, MAY 2019. Web of Science Citations: 1.
PALACIO ALVAREZ, MARCELA MACIEL; DE CARVALHO, RAFAEL GUZELLA; DE ARRUDA BARBOSA, SILVANA COELHO; POLASSI, MACKELER RAMOS; NASCIMENTO, FABIO DUPART; PERLATTI D'ALPINO, PAULO HENRIQUE; DOS SANTOS TERSARIOL, IVARNE LUIS. Oxidative stress induced by self-adhesive resin cements affects gene expression, cellular proliferation and mineralization potential of the MDPC-23 odontoblast-like cells. Dental Materials, v. 35, n. 4, p. 606-616, APR 2019. Web of Science Citations: 0.
DE SOUSA, J. P.; CARVALHO, R. G.; BARBOSA-MARTINS, L. F.; TORQUATO, R. J. S.; MUGNOL, K. C. U.; NASCIMENTO, F. D.; TERSARIOL, I. L. S.; PUPPIN-RONTANI, R. M. The Self-Assembling Peptide P-11-4 Prevents Collagen Proteolysis in Dentin. JOURNAL OF DENTAL RESEARCH, v. 98, n. 3, p. 347-354, MAR 2019. Web of Science Citations: 1.
DE GODOY, CARLOS M. G.; VASQUES, ENIO R.; CARICATI-NETO, AFONSO; TAVARES, JOSE G. P.; ALVES, BEATRIZ J.; DUARTE, JULIANA; MIRANDA-FERREIRA, REGIANE; LIMA, MARCELO A.; NADER, HELENA B.; DOS SANTOS TERSARIOL, IVARNE L. Heparin Oligosaccharides Have Antiarrhythmic Effect by Accelerating the Sodium-Calcium Exchanger. FRONTIERS IN CARDIOVASCULAR MEDICINE, v. 5, JUN 7 2018. Web of Science Citations: 3.
RAPHAELLI NAHAS-SCOCATE, ANA CARLA; ALVES DE MORAES, GABRIELLE FERRANTE; NADER, HELENA BONCIANI; VICENTE, CAROLINA MELONI; TOMA, LENY. Analysis of proteoglycan expression in human dental pulp. ARCHIVES OF ORAL BIOLOGY, v. 90, p. 67-73, JUN 2018. Web of Science Citations: 1.
LUCENA, SHEYLA V.; MOURA, GIOCONDA E. D. D.; RODRIGUES, TIAGO; WATASHI, CAROLINA M.; MELO, FABIANA H.; ICIMOTO, MARCELO Y.; VIANA, GUSTAVO M.; NADER, HELENA B.; MONTEIRO, HUGO P.; TERSARIOL, IVARNE L. S.; OGATA, FERNANDO T. Heparan sulfate proteoglycan deficiency up-regulates the intracellular production of nitric oxide in Chinese hamster ovary cell lines. Journal of Cellular Physiology, v. 233, n. 4, p. 3176-3194, APR 2018. Web of Science Citations: 0.
VICENTE, CAROLINA MELONI; DA SILVA, DAIANA APARECIDA; SARTORIO, PRISCILA VERONICA; SILVA, TIAGO DONIZETTI; SAAD, SARHAN SYDNEY; NADER, HELENA BONCIANI; FORONES, NORA MANOUKIAN; TOMA, LENY. Heparan Sulfate Proteoglycans in Human Colorectal Cancer. ANALYTICAL CELLULAR PATHOLOGY, 2018. Web of Science Citations: 3.
ALVAREZ, M. M. P.; MOURA, G. E.; MACHADO, M. F. M.; VIANA, G. M.; DE SOUZA COSTA, C. A.; TJADERHANE, L.; NADER, H. B.; TERSARIOL, I. L. S.; NASCIMENTO, F. D. PAR-1 and PAR-2 Expression Is Enhanced in Inflamed Odontoblast Cells. JOURNAL OF DENTAL RESEARCH, v. 96, n. 13, p. 1518-1525, DEC 2017. Web of Science Citations: 1.
CAVALHEIRO, R. P.; LIMA, M. A.; JARROUGE-BOUCAS, T. R.; VIANA, G. M.; LOPES, C. C.; COULSON-THOMAS, V. J.; DREYFUSS, J. L.; YATES, E. A.; TERSARIOL, I. L. S.; NADER, H. B. Coupling of vinculin to F-actin demands Syndecan-4 proteoglycan. MATRIX BIOLOGY, v. 63, p. 23-37, NOV 2017. Web of Science Citations: 7.
MOTTA, GUACYARA; TERSARIOL, IVARNE L. S. Modulation of the Plasma Kallikrein-Kinin System Proteins Performed by Heparan Sulfate Proteoglycans. FRONTIERS IN PHYSIOLOGY, v. 8, JUL 11 2017. Web of Science Citations: 5.
PERES, GIOVANI B.; SCHOR, NESTOR; MICHELACCI, YARA M. Impact of high glucose and AGEs on cultured kidney-derived cells. Effects on cell viability, lysosomal enzymes and effectors of cell signaling pathways. Biochimie, v. 135, p. 137-148, APR 2017. Web of Science Citations: 4.

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