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过氧亚硝酸盐修饰的DNA:系统性红斑狼疮抗DNA自身抗体的更佳抗原。

Peroxynitrite-modified DNA: a better antigen for systemic lupus erythematosus anti-DNA autoantibodies.

作者信息

Habib Safia, Ali Rashid

机构信息

Department of Biochemistry, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh 202002, India.

出版信息

Biotechnol Appl Biochem. 2006 Feb;43(Pt 2):65-70. doi: 10.1042/BA20050156.

DOI:10.1042/BA20050156
PMID:16232128
Abstract

Native human DNA was modified by ONOO- (peroxynitrite), generated by the synergistic action of sodium nitroprusside [Na2Fe(CN)5NO], an NO donor, and pyrogallol, a superoxide donor. The modifications were analysed by UV absorption characteristics, fluorescence emission transitions, nuclease S1 digestibility and melting-temperature studies. Modified DNA was found to be highly immunogenic, inducing high-titre immunogen-specific antibodies in experimental animals. A maximum of 85% inhibition of the antibody binding was observed in competition ELISA with immunogen as inhibitor. SLE (systemic lupus erythematosus) anti-DNA autoantibodies recognized modified DNA as a better antigen than the native analogue. Modification of native DNA by ONOO-, forming neo-epitopes on the molecule, may be one of the factors for the induction of the autoimmune response seen in SLE.

摘要

天然人类DNA被过氧亚硝酸根(ONOO-)修饰,过氧亚硝酸根由一氧化氮供体硝普钠[Na2Fe(CN)5NO]和超氧阴离子供体邻苯三酚的协同作用产生。通过紫外线吸收特性、荧光发射跃迁、核酸酶S1消化率和熔解温度研究对这些修饰进行了分析。发现修饰后的DNA具有高度免疫原性,能在实验动物中诱导产生高滴度的免疫原特异性抗体。在以免疫原为抑制剂的竞争ELISA中,观察到抗体结合的最大抑制率为85%。系统性红斑狼疮(SLE)抗DNA自身抗体将修饰后的DNA识别为比天然类似物更好的抗原。ONOO-对天然DNA的修饰在分子上形成新表位,可能是SLE中所见自身免疫反应诱导的因素之一。

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