Modification of histone by glyoxal: recognition of glycated histone containing advanced glycation adducts by serum antibodies of type 1 diabetes patients

Abstract Dicarbonyl compounds react more rapidly, than glucose, with arginine and lysine in proteins to form advanced glycation end products (AGEs) and further produce free radicals which cause DNA damage. AGEs are reliable diagnostic biomarkers for most of the age-related diseases. In the present s...

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Bibliographic Details
Published in:Glycobiology (Oxford) 2018-04, Vol.28 (4), p.207-213
Main Authors: Ansari, Nadeem Ahmad, Chaudhary, Dharmendra Kumar, Dash, Debabrata
Format: Article
Language:English
Subjects:
Antibodies - blood
Antibodies - metabolism
Diabetes Mellitus, Type 1 - blood
Diabetes Mellitus, Type 1 - metabolism
Enzyme-Linked Immunosorbent Assay
Glycation End Products, Advanced - chemistry
Glycation End Products, Advanced - metabolism
Glycosylation
Glyoxal - chemistry
Glyoxal - metabolism
Histones - chemistry
Histones - metabolism
Humans
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Summary:Abstract Dicarbonyl compounds react more rapidly, than glucose, with arginine and lysine in proteins to form advanced glycation end products (AGEs) and further produce free radicals which cause DNA damage. AGEs are reliable diagnostic biomarkers for most of the age-related diseases. In the present study histone was modified with glyoxal and it was characterized by various spectral techniques. Binding characteristics of the modified histone towards serum antibodies from type 1 diabetes patients was evaluated by solid phase enzyme immunoassay and the results were compared with normal human subjects. Fluorescence and Fourier transformed infrared analysis of the nuclear protein clearly indicated changes in their respective intensities upon modification with glyoxal. Liquid chromatography together with mass spectrometry showed new peaks and m/z values related to AGE adducts of dihydroimidazolidines/hydroimidazolones. This glyoxal modified protein was recognized by serum antibodies of the diabetes patients while it showed negligible binding with that of normal human subjects. Glyoxal modification of histone causes structural turbulence and formation of advanced glycation adducts in histone. These adducts might be the main antigenic epitope of the modified histone, leading to its recognition by circulating type 1 diabetes antibodies.
ISSN:0959-6658
1460-2423
1460-2423
DOI:10.1093/glycob/cwy006