Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
Department of Molecular Medicine & Biotechnology, SGPGIMS, Lucknow 226014, India.
Glycobiology. 2018 Apr 1;28(4):207-213. doi: 10.1093/glycob/cwy006.
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.
二羰基化合物与精氨酸和赖氨酸在蛋白质中的反应速度比葡萄糖更快，形成晚期糖基化终产物（AGEs），并进一步产生自由基，导致 DNA 损伤。AGEs 是大多数与年龄相关疾病的可靠诊断生物标志物。在本研究中，组蛋白被乙二醛修饰，并通过各种光谱技术进行了表征。通过固相酶免疫测定法评估了修饰组蛋白与 1 型糖尿病患者血清抗体的结合特性，并将结果与正常人进行了比较。荧光和傅里叶变换红外分析表明，核蛋白的相应强度在乙二醛修饰后发生了变化。液相色谱与质谱联用显示了与二氢咪唑烷/羟咪唑酮的 AGE 加合物相关的新峰和 m/z 值。这种乙二醛修饰的蛋白质被糖尿病患者的血清抗体识别，而与正常人的血清抗体几乎没有结合。组蛋白的乙二醛修饰会导致组蛋白结构的混乱和晚期糖基化加合物的形成。这些加合物可能是修饰组蛋白的主要抗原表位，导致其被循环的 1 型糖尿病抗体识别。
