Hydroxyl radical modification of polyguanylic acid: Role of modified guanine in circulating SLE anti-DNA autoantibodies
Hydroxyl radical modification of polyguanylic acid: Role of modified guanine in circulating SLE anti-DNA autoantibodies
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DOI：
10.1081/imm-120022978
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发表时间：
2003-01-01
影响因子：
2.8
通讯作者：
Ali, R
中科院分区：
文献类型：
--
作者：
Garg, DK;Moinuddin;Ali, R
用分光光度法、琼脂糖凝胶电泳法、Sephadex G-200凝胶过滤法和DEAE Sephadex A-25柱层析法研究了过氧化氢辐射产生的羟基自由基对核均聚物、聚鸟氨酸、聚(G)鸟嘌呤残基的损伤作用。天然和ROS-Poly(G)具有较强的免疫原性，可诱导兔产生高滴度抗体。抗体与呈现B-、A-和相关构象的各种合成多核苷酸显示出广泛的交叉反应。诱导抗体的不同抗原结合特性类似于自然产生的狼疮抗DNA自身抗体。不同SLE患者的血清与ROS-Poly(G)的结合优先于天然Poly(G)，这表明氧化修饰的鸟嘌呤残基被更好地识别。讨论了这些发现在氧自由基修饰的DNA鸟嘌呤残基诱导SLE抗DNA自身抗体中的意义。
The hydroxyl radical generated by UV irradiation of hydrogen peroxide cause an extensive damage to guanine residues of ribohomopolymer, polyguanylic acid, poly (G) as investigated by spectrophotometric measurements, agarose gel electrophoresis, Sephadex G-200 gel filtration and DEAE Sephadex A-25 column chromatography. Native and ROS-poly (G) were highly immunogenic inducing high titre antibodies in rabbits. The antibodies showed wide range of cross reactivity with various synthetic polynucleotides exhibiting B-, A-, and allied conformations. The diverse antigen binding characteristics of the induced antibodies resembles to those of naturally occurring lupus anti-DNA autoantibodies. Sera from various SLE patients showed preferential binding to ROS-poly (G) than native poly (G), indicating that oxidatively modified guanine residues are better recognised. The significance of these findings in the induction of SLE anti-DNA autoantibodies by oxygen free radicals modified guanine residues in DNA has been discussed.