title: Immunogenicity of DNA-advanced glycation end product fashioned through glyoxal and arginine in the presence of Fe³⁺: its potential role in prompt recognition of diabetes mellitus auto-antibodies.
abstract: Glyoxal, methylglyoxal and 3-deoxyglucosones are reactive dicarbonyl compounds, which transform free amino groups of proteins and lipoproteins macromolecule into advanced glycation end-products (AGEs). AGEs play a significant role in the pathophysiology of aging and diabetic complications because of their genotoxic effect. Glyoxal also reacts with free amino group of nucleic acids resulting in the formation of DNA-AGEs. The present study reports the genotoxicity and immunogenicity of AGEs formed by Glyoxal-Arginine-Fe(3+) (G-Arg-Fe(3+)) system as a glycating agent. Immunogenicity of native and G-Arg-Fe(3+)-DNA was probed in female rabbits. Immunofluorescence suggests the presence of immune complex deposition in the kidney section of immunized rabbits. Spectroscopic analysis and melting temperature indicates the structural modification in the human DNA. The modified human DNA is found to be highly immunogenic, whereas unmodified form was simply non-immunogenic. This study shows the presence of auto-antibodies against G-Arg-Fe(3+) modified human DNA in the sera of diabetes type 1 and in few cases type 2 patients due to secondary complications of nephropathy. The glyco-oxidative lesions have also been detected in the lymphocyte DNA isolated from patients having type 1 and type 2 diabetes. The results show structural perturbations generating new epitopes in G-Arg-Fe(3+)-DNA rendering it pretty immunogenic.
authors: Department of Biochemistry, Central Drug Research Institute, Lucknow, U.P., India; Department of Biochemistry, King George Medical University, Lucknow, U.P., India.
authors: Uzma
authors: U
authors: Shahab
authors: King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Shams
authors: S
authors: Tabrez
authors: Department of Biosciences, Integral University, Lucknow, U.P., India.
authors: M Salman
authors: MS
authors: Khan
authors: Department of Biosciences, Integral University, Lucknow, U.P., India.
authors: Firoz
authors: F
authors: Akhter
authors: Department of Biosciences, Integral University, Lucknow, U.P., India.
authors: Mohd Sajid
authors: MS
authors: Khan
authors: Department of Biosciences, Integral University, Lucknow, U.P., India.
authors: Mohd
authors: M
authors: Saeed
authors: Department of Biosciences, Integral University, Lucknow, U.P., India.
authors: Khurshid
authors: K
authors: Ahmad
authors: Department of Biosciences, Integral University, Lucknow, U.P., India.
authors: A K
authors: AK
authors: Srivastava
authors: Department of Biosciences, Integral University, Lucknow, U.P., India. Electronic address: ahmadsaheem@gmail.com.
authors: Saheem
authors: S
authors: Ahmad
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology*; D001120:Arginine / Q000494:pharmacology; D002942:Circular Dichroism; D020552:Comet Assay; D004247:DNA / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000097:blood / Q000276:immunology*; D003928:Diabetic Nephropathies / Q000097:blood / Q000276:immunology*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D017127:Glycation End Products, Advanced / Q000097:blood / Q000276:immunology* / Q000648:ultrastructure; D006037:Glyoxal / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear; D008856:Microscopy, Fluorescence; D011817:Rabbits; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000936:Antigen-Antibody Complex; D001120:Arginine; D004247:DNA; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D006037:Glyoxal
keywords: Advanced glycation end products (AGEs); Diabetes mellitus type 1 and 2; Genotoxicity; Glycation; Glyoxal; Immunogenicity