Abdul Rouf Mir
University of Kashmir, India
Title: Histone glycoxidation and its role in Cancer autoimmunity
Biography
Biography: Abdul Rouf Mir
Abstract
The emerging correlation of AGE-RAGE axis with cancers has led researchers to study the role of sugars and their by-products as potential relevant mediators. Where, some workers have established the association between hypergycemia and cancer by investigating AGEs in blood circulation, our group has observed a strong autoimmune response against neo-epitopes generated upon histone proteins due to glycoxidation induced structural perturbations. In this study, we report the methylglyoxal induced conformational changes in histone H1 and H2A leading to modifications in the aromatic residues, changed tyrosine microenvironment, intermolecular cross linking and generation of AGEs, masking of hydrophobic patches and a hypsochromic shift in the in ANS specific fluorescence, amorphous aggregation, thermal stability and the formation of Nε-(carboxyethyl)lysine. Modified histones induced high titre antibodies in rabbits and the IgG isolated form sera of rabbits immunized with modified histones exhibited specific binding with their immunogens in Western Blot analysis. IgG isolated from the sera of patients with different types of cancers showed better recognition for neo-epitopes on the modified histones in ELISA and gel retardation assay, reflecting the presence of circulating autoantibodies in cancer against glycoxidatively modified histones in cancer patients. Keeping in view the role of protein post translational modifications in stimulating cellular and humoral immune responses, methylglyoxal modified histones may also be considered as potential antigenic candidates for eliciting autoimmune response in cancer patients.