Enhanced binding of circulating SLE autoantibodies to catecholestrogen-copper-modified DNA.
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by circulating and tissue fixed autoantibodies reactive with self-antigens, including nucleic acid and other nuclear components. The pathways by which these autoantibodies act as a pathogenic factor remain elusive. Present study has investigated the role of estrogens in SLE etiopathogenesis. Estrogen-modified DNA [4-OHE(2)-Cu(II)-DNA] showed single- and double-strand breaks, hyperchromicity, decrease in Tm, and modification of bases. The 4-OHE(2)-Cu(II)-DNA exhibited increased binding with naturally occurring anti-DNA autoantibodies as compared to the unmodified native form (P < 0.001) as assessed by ELISA, quantitative precipitin titration, and gel retardation assay. The relative affinity of anti-DNA antibodies for modified and native DNA was in the order of 2.1 x 10(-7) M and 1.3 x 10(-6) M, respectively. The data suggested that DNA modified with 4-OHE(2) and Cu(II) may be one of the factors for the induction of circulating anti-DNA autoantibodies in SLE.
Khan
Wahid Ali
WA
Department of Biochemistry, J. N. Medical College, A. M. U., Aligarh, 202002, India.
Habib
Safia
S
Khan
Wajid Ali
WA
Alam
Khursheed
K
Moinuddin
D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology*; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000276:immunology*; D004587:Electrophoresis, Agar Gel; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D002393:Estrogens, Catechol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007700:Kinetics; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D009691:Nucleic Acid Denaturation / Q000187:drug effects; D011485:Protein Binding; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D002393:Estrogens, Catechol; D003300:Copper; D004247:DNA