Abstract
Glycation initiates with the non-enzymatic reaction of amino group of proteins and lipoproteins by carbonyl group of sugar moiety and intermediates of glycative stress such as methylglyoxal (MG). The initial glycation leads to the formation of early glycation products (Amadori products) which undergo rearrangement, cyclization and dehydration to form advanced glycation end products (AGEs). The main objective of the present study is to investigate the non-enzymatic glycation of low density lipoprotein (LDL) by MG at different concentration and at increasing incubation time period in vitro. This modification may increase the formation of Amadori products and AGEs which are physico-chemically characterized with respect to the extent of LDL modification. Additionally, immunogenicity of native and MG modified LDL (MG-LDL) was probed in female rabbits in vivo. Immunogenicity of MG-LDL was found to be highly immunogenic, eliciting high titer immunogen-specific antibodies while native form of LDL is less immunogenic. Furthermore, the histopathology and immune-fluorescence studies suggest that the kidney section of immunized rabbits exhibit the presence of immune complex (MG-LDL-IgG) deposition in the glomerular basement membrane (GBM).
•Glycation of LDL by methylglyoxal (MG-LDL) alters the structural integrity of the LDL macromolecule.•Biochemical assay hints the increased ketoamines, carbonyls, TBARS and HMF content in MG-LDL as compared to native analogue.•MG-LDL causing generation of neo‐antigenic epitopes which was found to be highly immunogenic in experimental animals.•The induced antibodies exhibited wide range of heterogeneity and poly-specificity against MG-LDL.