The melibiose-derived glycation product mimics a unique epitope present in human and animal tissues

Abstract Non-enzymatic modification of proteins by carbohydrates, known as glycation, leads to generation of advanced glycation end-products (AGEs). In our study we used in vitro generated AGEs to model glycation in vivo. We discovered in vivo analogs of unusual melibiose-adducts designated MAGEs (m...

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Main Authors: Magdalena Staniszewska, Agnieszka Bronowicka-Szydełko, Kinga Gostomska-Pampuch, Jerzy Szkudlarek, Arkadiusz Bartyś, Tadeusz Bieg, Elżbieta Gamian, Agata Kochman, Bolesław Picur, Jadwiga Pietkiewicz, Piotr Kuropka, Wiesław Szeja, Jerzy Wiśniewski, Piotr Ziółkowski, Andrzej Gamian
Format: Article
Language:English
Published: Nature Portfolio 2021-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-82585-7
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author Magdalena Staniszewska
Agnieszka Bronowicka-Szydełko
Kinga Gostomska-Pampuch
Jerzy Szkudlarek
Arkadiusz Bartyś
Tadeusz Bieg
Elżbieta Gamian
Agata Kochman
Bolesław Picur
Jadwiga Pietkiewicz
Piotr Kuropka
Wiesław Szeja
Jerzy Wiśniewski
Piotr Ziółkowski
Andrzej Gamian
author_facet Magdalena Staniszewska
Agnieszka Bronowicka-Szydełko
Kinga Gostomska-Pampuch
Jerzy Szkudlarek
Arkadiusz Bartyś
Tadeusz Bieg
Elżbieta Gamian
Agata Kochman
Bolesław Picur
Jadwiga Pietkiewicz
Piotr Kuropka
Wiesław Szeja
Jerzy Wiśniewski
Piotr Ziółkowski
Andrzej Gamian
author_sort Magdalena Staniszewska
collection DOAJ
description Abstract Non-enzymatic modification of proteins by carbohydrates, known as glycation, leads to generation of advanced glycation end-products (AGEs). In our study we used in vitro generated AGEs to model glycation in vivo. We discovered in vivo analogs of unusual melibiose-adducts designated MAGEs (mel-derived AGEs) synthesized in vitro under anhydrous conditions with bovine serum albumin and myoglobin. Using nuclear magnetic resonance spectroscopy we have identified MAGEs as a set of isomers, with open-chain and cyclic structures, of the fructosamine moiety. We generated a mouse anti-MAGE monoclonal antibody and show for the first time that the native and previously undescribed analogous glycation product exists in living organisms and is naturally present in tissues of both invertebrates and vertebrates, including humans. We also report MAGE cross-reactive auto-antibodies in patients with diabetes. We anticipate our approach for modeling glycation in vivo will be a foundational methodology in cell biology. Further studies relevant to the discovery of MAGE may contribute to clarifying disease mechanisms and to the development of novel therapeutic options for diabetic complications, neuropathology, and cancer.
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spelling doaj.art-5e928347233642c5a6d161c60deb78d82022-12-21T21:46:21ZengNature PortfolioScientific Reports2045-23222021-02-0111111310.1038/s41598-021-82585-7The melibiose-derived glycation product mimics a unique epitope present in human and animal tissuesMagdalena Staniszewska0Agnieszka Bronowicka-Szydełko1Kinga Gostomska-Pampuch2Jerzy Szkudlarek3Arkadiusz Bartyś4Tadeusz Bieg5Elżbieta Gamian6Agata Kochman7Bolesław Picur8Jadwiga Pietkiewicz9Piotr Kuropka10Wiesław Szeja11Jerzy Wiśniewski12Piotr Ziółkowski13Andrzej Gamian14Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of SciencesDepartment of Medical Biochemistry, Wroclaw Medical UniversityHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of SciencesHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of SciencesHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of SciencesDepartment of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of TechnologyDepartment of Pathomorphology, Wroclaw Medical UniversityDepartment of Pathology, University Hospital MonklandsFaculty of Chemistry, University of WrocławDepartment of Medical Biochemistry, Wroclaw Medical UniversityDepartment of Anatomy and Histology, Wroclaw University of Environmental and Life SciencesDepartment of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of TechnologyDepartment of Medical Biochemistry, Wroclaw Medical UniversityDepartment of Pathomorphology, Wroclaw Medical UniversityHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of SciencesAbstract Non-enzymatic modification of proteins by carbohydrates, known as glycation, leads to generation of advanced glycation end-products (AGEs). In our study we used in vitro generated AGEs to model glycation in vivo. We discovered in vivo analogs of unusual melibiose-adducts designated MAGEs (mel-derived AGEs) synthesized in vitro under anhydrous conditions with bovine serum albumin and myoglobin. Using nuclear magnetic resonance spectroscopy we have identified MAGEs as a set of isomers, with open-chain and cyclic structures, of the fructosamine moiety. We generated a mouse anti-MAGE monoclonal antibody and show for the first time that the native and previously undescribed analogous glycation product exists in living organisms and is naturally present in tissues of both invertebrates and vertebrates, including humans. We also report MAGE cross-reactive auto-antibodies in patients with diabetes. We anticipate our approach for modeling glycation in vivo will be a foundational methodology in cell biology. Further studies relevant to the discovery of MAGE may contribute to clarifying disease mechanisms and to the development of novel therapeutic options for diabetic complications, neuropathology, and cancer.https://doi.org/10.1038/s41598-021-82585-7
spellingShingle Magdalena Staniszewska
Agnieszka Bronowicka-Szydełko
Kinga Gostomska-Pampuch
Jerzy Szkudlarek
Arkadiusz Bartyś
Tadeusz Bieg
Elżbieta Gamian
Agata Kochman
Bolesław Picur
Jadwiga Pietkiewicz
Piotr Kuropka
Wiesław Szeja
Jerzy Wiśniewski
Piotr Ziółkowski
Andrzej Gamian
The melibiose-derived glycation product mimics a unique epitope present in human and animal tissues
Scientific Reports
title The melibiose-derived glycation product mimics a unique epitope present in human and animal tissues
title_full The melibiose-derived glycation product mimics a unique epitope present in human and animal tissues
title_fullStr The melibiose-derived glycation product mimics a unique epitope present in human and animal tissues
title_full_unstemmed The melibiose-derived glycation product mimics a unique epitope present in human and animal tissues
title_short The melibiose-derived glycation product mimics a unique epitope present in human and animal tissues
title_sort melibiose derived glycation product mimics a unique epitope present in human and animal tissues
url https://doi.org/10.1038/s41598-021-82585-7
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