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

Affiliation

Staniszewska M(1)(2), Bronowicka-Szydełko A(3), Gostomska-Pampuch K(1)(3), Szkudlarek J(1), Bartyś A(1), Bieg T(4), Gamian E(5), Kochman A(6), Picur B(7), Pietkiewicz J(3), Kuropka P(8), Szeja W(4), Wiśniewski J(3), Ziółkowski P(5), Gamian A(9)(10)(11).
Author information:
(1)Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wrocław, Poland.
(2)Centre for Interdisciplinary Research, The John Paul II Catholic University of Lublin, Konstantynow 1J, 20-708, Lublin, Poland.
(3)Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368, Wrocław, Poland.
(4)Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of Technology, Krzywoustego 4, 44-100, Gliwice, Poland.
(5)Department of Pathomorphology, Wroclaw Medical University, Marcinkowskiego 1, 50-368, Wrocław, Poland.
(6)Department of Pathology, University Hospital Monklands, Monkscourt Ave, Airdrie, ML6 0JS, UK.
(7)Faculty of Chemistry, University of Wrocław, 50-383, Wrocław, Poland.
(8)Department of Anatomy and Histology, Wroclaw University of Environmental and Life Sciences, Norwida 1, 50-375, Wrocław, Poland.
(9)Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114, Wrocław, Poland. [Email]
(10)Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368, Wrocław, Poland. [Email]
(11)Wroclaw Research Centre EIT+, PORT, Stabłowicka 147/149, 54-066, Wrocław, Poland. [Email]

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.