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来自多发性硬化症患者血液和脑脊液的多克隆抗体可有效水解DNA和RNA。

Polyclonal antibodies from blood and cerebrospinal fluid of patients with multiple sclerosis effectively hydrolyze DNA and RNA.

作者信息

Baranovskii A G, Kanyshkova T G, Mogelnitskii A S, Naumov V A, Buneva V N, Gusev E I, Boiko A N, Zargarova T A, Favorova O O, Nevinsky G A

机构信息

Novosibirsk Institute of Bioorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia.

出版信息

Biochemistry (Mosc). 1998 Nov;63(11):1239-48.

PMID:9864461
Abstract

It is known that in the blood of patients with some autoimmune diseases catalytically active antibodies hydrolyzing proteins, DNA, and RNA may be detected. In the present work homogeneous preparations of IgG antibodies (Ab) possessing high affinity for nucleic acids (NA) were obtained for the first time from blood and cerebrospinal fluid of patients with multiple sclerosis (MS). The fraction of IgG Ab as well as its Fab fragments and isolated light chains of both kappa- and lambda-types were shown to catalyze effectively the hydrolysis of DNA and RNA. It is shown by different methods that the capability for nucleic acid hydrolysis is an intrinsic property of the polyclonal Ab. NA-hydrolyzing Ab were detected in the blood of 69 of 72 and in the cerebrospinal fluid of 5 of 5 examined MS patients, while they were not detected in the blood of any of 50 healthy donors examined. Comparison of relative rates of RNA hydrolysis and of the substrate specificity in hydrolysis of various model RNAs--cCMP, poly(U), poly(A), and poly(C)--revealed pronounced differences of MS antibodies from ribonucleases of human blood, ribonuclease A, and all earlier described abzymes. The abzymes are usually characterized by relatively low specific activities in comparison with that of normal enzymes catalyzing analogous reactions. Ab from the blood of MS patients are the first example of autoabzymes whose specific activity in RNA hydrolysis is comparable or even higher than that of pancreatic ribonuclease A--one of the most active RNA-hydrolyzing enzymes.

摘要

已知在一些自身免疫性疾病患者的血液中可检测到能催化水解蛋白质、DNA和RNA的活性抗体。在本研究中,首次从多发性硬化症(MS)患者的血液和脑脊液中获得了对核酸(NA)具有高亲和力的IgG抗体(Ab)的纯化物。结果表明,IgG Ab组分及其Fab片段以及κ型和λ型的分离轻链均能有效催化DNA和RNA的水解。通过不同方法表明,核酸水解能力是多克隆Ab的固有特性。在72例受检MS患者中的69例血液以及5例受检患者的脑脊液中检测到了核酸水解Ab,而在50例健康供者的血液中均未检测到。比较RNA水解的相对速率以及各种模型RNA(cCMP、聚(U)、聚(A)和聚(C))水解中的底物特异性,发现MS抗体与人血核糖核酸酶、核糖核酸酶A以及所有先前描述的抗体酶有明显差异。与催化类似反应的正常酶相比,抗体酶通常具有相对较低的比活性。MS患者血液中的Ab是自身抗体酶的首个例子,其在RNA水解中的比活性与胰腺核糖核酸酶A(最具活性的RNA水解酶之一)相当甚至更高。

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