Enhanced binding of lupus sera to the polyamine-induced left-handed Z-DNA form of polynucleotides.
The natural polyamines putrescine, spermidine, and spermine are small polyvalent cations present in all living cells. Spermidine and spermine are excellent promoters of left-handed Z-DNA, an immunogenic form of DNA that binds readily with anti-DNA antibodies in the sera of patients with systemic lupus erythematosus (SLE). We studied the binding of a panel of 16 SLE sera to poly(dA-dC).poly(dG-dT) and poly(dG-m5dC).poly(dG-m5dC) in the presence and absence of spermidine and spermine using an enzyme-linked immunosorbent assay. The majority of SLE sera showed a 50-150% mean increase in optical density values when incubated with the polynucleotides and either 0.25 mM spermidine or 0.025 mM spermine than when incubated with the polynucleotides alone. Under these conditions, the polynucleotides assumed the Z-DNA form. Since polyamines are ubiquitous cellular components and since potential Z-DNA-forming alternating purine-pyrimidine sequences are widely dispersed in native DNA, the increased binding of SLE sera to polyamine-induced Z-DNA suggests a pathogenic role for these compounds in SLE.
Thomas
T J
TJ
Division of Rheumatology, University of Medicine and Dentistry, New Brunswick 08903-0019.
Meryhew
N L
NL
Messner
R P
RP
D001323:Autoantibodies / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D004247:DNA / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology; D011073:Polyamines / Q000378:metabolism / Q000494:pharmacology*; D011119:Polynucleotides / Q000276:immunology / Q000378:metabolism*; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology
D001323:Autoantibodies; D007074:Immunoglobulin G; D011073:Polyamines; D011119:Polynucleotides; D013096:Spermine; D004247:DNA; D013095:Spermidine