Immunogenicity of mitochondrial DNA modified by hydroxyl radical

Immunogenicity of mitochondrial DNA modified by hydroxyl radical
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DOI:
10.1016/j.cellimm.2007.06.007
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发表时间:
2007-05-01
影响因子:
4.3
通讯作者:
Jabeen, Suraya
Jabeen, Suraya
中科院分区:
医学4区
文献类型:
--
作者:
Alam, Khurshid;Moinuddin;Jabeen, Suraya

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线粒体消耗人体所用氧气的90%,是活性氧(ROS)的特别丰富的来源。本研究从新鲜山羊肝脏中提取线粒体DNA,并利用紫外线照射产生的羟基自由基(254过氧化氢)对线粒体DNA进行体外修饰。作为羟基自由基修饰的结果,线粒体DNA表现出增色性和敏感性核酸酶S-I消化相比,控制mtDNA。直接结合法和竞争ELISA法检测线粒体DNA和ROS修饰的线粒体DNA免疫动物诱导的抗体。结果表明,经羟基自由基处理后,线粒体DNA的免疫原性增强。从免疫血清中分离的IgG对相应的免疫原具有特异性,并与其他核酸有交叉反应。诱导的抗体与抗原阵列的结合清楚地表明其多特异性性质。此外,诱导的抗体所表现出的多特异性是独特的,因为来自SLE患者的天然存在的抗DNA抗体具有相似的多抗原结合特性。(C)2007年爱思唯尔公司All rights reserved.
Mitochondria consume about 90 percent of oxygen used by the body, and are a particularly rich source of reactive oxygen species (ROS). In this research communication mitochondrial DNA (mtDNA) was isolated from fresh goat liver and modified in vitro by hydroxyl radical generated from UV irradiation (254 rival of hydrogen peroxide. As a consequence of hydroxyl radical modification, mtDNA showed hyperchromicity and sensitivity to nuclease S I digestion as compared to control mtDNA. Animals immunized with mtDNA and ROS-modified mtDNA induced antibodies as detected by direct binding and competition ELISA. The data suggest that immunogenicity of mtDNA got augmented after treatment with hydroxyl radical. IgG isolated from immune sera showed specificity for respective immunogen and cross-reaction with other nucleic acids. Binding of induced antibodies with array of antigens clearly indicates their polyspecific nature. Moreover, the polyspecificity exhibited by induced antibodies is unique in view of similar multiple antigen binding properties of naturally occurring anti-DNA antibodies derived from SLE patients. (C) 2007 Elsevier Inc. All rights reserved.