Methylglyoxal mediated conformational changes in histone H2A—generation of carboxyethylated advanced glycation end products

Neo-Epitopes Generated on Hydroxyl Radical Modified GlycatedIgG Have Role in Immunopathology of Diabetes Type 2

“…The78.3% hyperchromicity in UV absorbance values forOH • -MG modifiedIgGas compared to 55.9% and 64.7% for OH • -IgG and MG-IgG samples, when compared with N-IgG, suggests a stronger structural damage of IgG by OH • -MG. IgG modified by OH • -MG reflect highly exposed chromophoric aromatic amino acid residues, indicating extensive structural perturbations in the molecule.Appearance of a hump like structure in MG-IgG and OH • -MG-IgG indicate the formation of AGEs. Similar changes in absorbance have been reported earlier[45, 46]. Fluorescence spectroscopy is a valuable parameter to monitor microenvironment around aromatic amino acid residues [47].…”

Glycoxidation of histone proteins in autoimmune disorders

“…Various methods for glycation studies have been developed and a variety of procedures for estimating the generation of advanced glycation by-products in histones have been formulated. Many modification sites have been detected and sequenced [12,13,[19][20][21][22][23][24][25][26]. Many conformational changes induced by glyoxidation reactions have been reported with roles in a variety of pathological complications [22,25,45,51,52,63].…”

“…The alterations in the histone proteins have been studied using various biophysical and biochemical techniques like radio-labelling [19], NMR spectroscopy [19], fluorescence spectroscopy [20,21], fourier transform infrared spectroscopy [20,21], circular dichroism [20,22], Xray irradiation [23], electrophoresis [20,21,24], Western blotting [12], immunoassays [25], liquid chromatography-mass spectrometry (LC-MS) and matrix-assisted laser desorption/ionization (MALDI-MS/ MS) [13], and reversed-phase HPLC [26] It was in late 70s and in 80s that some workers suggested Schiff base formation and browning reactions in histone proteins on the pattern of other glycated proteins, thus opening vistas of studies on glyoxidative damage to nuclear proteins [27][28][29][30][31][32][33]. The term 'glycohistone' was coined by Jobst et al in 1991 after they detected histone glycation in hepatic nuclei of patients dying of decompensated diabetes [34].…”

“…Earlier, we demonstrated methylglyoxal inducing hyperchromicity, loss in intrinsic tyrosine fluorescence along with a red shift, destruction or modification of tyrosine microenvironment, induction of α helix, increase in the electrophoretic mobility, cross linking and dimer formation, formation of more ordered secondary structure and increased compactness in histone H2A. It led to the masking of protein hydrophobic patches, accumulation of AGEs, increase in the protein carbonyls, generation of carboxyethyllysine, enhanced thermodynamic stability (Tm) and enhanced heat capacities (Cp) in the glycated histones [20]. Methylglyoxal mediated glycation of histones has been observed with implications in patients with type 1 diabetes mellitus [50].…”

A clinical correlation of anti-DNA-AGE autoantibodies in type 2 diabetes mellitus with disease duration

“…DM results either due to lack of insulin or because of the presence of factors that oppose the action of insulin. It is well recognized that long-term exposure of macromolecules during hyperglycemia results in excessive nonenzymatic glycation and formation of advanced glycation end products (AGEs) [2][3][4][5][6]. Furthermore, chronic hyperglycemia may accelerate AGE formation in different tissues [7].…”