Cargando…

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

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-derive...

Descripción completa

Detalles Bibliográficos
Autores principales: Staniszewska, Magdalena, Bronowicka-Szydełko, Agnieszka, Gostomska-Pampuch, Kinga, Szkudlarek, Jerzy, Bartyś, Arkadiusz, Bieg, Tadeusz, Gamian, Elżbieta, Kochman, Agata, Picur, Bolesław, Pietkiewicz, Jadwiga, Kuropka, Piotr, Szeja, Wiesław, Wiśniewski, Jerzy, Ziółkowski, Piotr, Gamian, Andrzej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859244/
https://www.ncbi.nlm.nih.gov/pubmed/33536563
http://dx.doi.org/10.1038/s41598-021-82585-7
Descripción
Sumario: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.