GOLGI COMPLEX ANTIBODIES AND AUTOANTIGENS

高尔基复合体抗体和自身抗原

基本信息

批准号：
6728217
负责人：
EDWARD K CHAN
金额：
$ 25.46万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-09-01 至 2006-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6728217
关键词：
Golgi apparatus RNA virus autoantigens autoimmune disorder gene expression laboratory mouse laboratory rabbit molecular pathology

项目摘要

Autoantibodies to the Golgi complex are found primarily in patients with Sjgren's syndrome and SLE although they are not restricted to these diseases. This competitive renewal application requests funding for the continuation of studies to characterize autoantigens of the Golgi complex and address the mechanisms that lead to the expression of autoantibodies to these intracellular organelle-associated proteins. The P.I.'s laboratory has been responsible for the identification of a family of Golgi antigens known as golgins. Common features of these autoantigens are that they are located on the cytoplasmic face of the Golgi cisternae and they have multiple alpha-helical coiled-coil rod domains flanked by non-coiled-coil and C- terminal domains. The goal of the proposed studies is to determine if the common structure and function for members of this protein family can explain the origin and production of autoantibodies in disease states. Specific Aim 1 will examine common features of golgins that may explain why they are targets of human anti-Golgi autoantibodies. The P.I. will characterize the events associated with the Golgi complex and golgins and their stability during apoptosis and necrosis. Hypotheses on how these autoantibodies may be produced in experimental models will be examined. Specific Aim 2 will examine if Golgi fragments and vesicular structures will induce immune and autoimmune response in experimental mice. Specific Aim 3 will elucidate the target of Golgi complex in lactate dehydrogenase-elevating virus (LDV) infected mice and address mechanism of how autoimmune response to the Golgi complex can be produced in these mice. Earlier studies have shown that LDV infected mice produce anti-Golgi antibodies. Our current data suggest that the autoimmune response to cytoplasmic organelles such as the Golgi complex is uniquely different from other intracellular autoantigens examined to date. It is anticipated that testing of the P.I.'s hypotheses will provide new insights into autoimmunity and autoimmune diseases associated with subcellular organelles.

高尔基体复合体的自身抗体主要在SJ Gren综合征和SLE患者中发现，尽管它们不限于这些疾病。这项竞争性更新应用要求提供资金继续研究，以表征高尔基体络合物的自身抗原，并解决导致自身抗体表达对这些细胞内细胞内细胞器相关蛋白的机制。 P.I.的实验室负责鉴定一个被称为Golgins的高尔基抗原家族。这些自动抗原的常见特征是它们位于高尔基硫酸盐的细胞质面上，并且它们具有多个alpha螺旋螺旋线圈杆域，该杆侧面是非覆盖型螺旋和c-末端域的侧面。拟议研究的目的是确定该蛋白质家族成员的共同结构和功能是否可以解释疾病状态中自身抗体的起源和产生。特定的目标1将检查戈尔金人的共同特征，这些特征可能解释了为什么它们是人类抗高尔基体自身抗体的靶标。 P.I.将表征与高尔基复合物和高尔金有关的事件及其在凋亡和坏死过程中的稳定性。将研究如何在实验模型中产生这些自身抗体的假设。特定的目标2将检查高尔基体片段和囊泡结构是否会在实验小鼠中诱导免疫和自身免疫反应。具体的目标3将阐明高尔基络合物在乳酸脱氢酶催化病毒（LDV）感染小鼠中的靶标，并解决如何在这些小鼠中产生自身免疫反应对高尔基体复合物的机制。早期的研究表明，LDV感染的小鼠产生抗高尔基抗体。我们当前的数据表明，对胞质细胞器（例如高尔基体配合物）的自身免疫反应与迄今为止检查的其他细胞内自身抗原截然不同。预计对P.I.假设的测试将提供有关与亚细胞细胞器相关的自身免疫性和自身免疫性疾病的新见解。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Differential anti-Golgi complex autoantibody production following murine lactate dehydrogenase-elevating virus infection.

鼠乳酸脱氢酶升高病毒感染后差异性抗高尔基复合体自身抗体的产生。

DOI：
10.1080/08923970701812191
发表时间：
2008
期刊：
Immunopharmacology and immunotoxicology
影响因子：
3.3
作者：
Nozawa,Kazuhisa;Fritzler,MarvinJ;Ikeda,Keigo;Takasaki,Yoshinari;Satoh,Minoru;Chan,EdwardKL
通讯作者：
Chan,EdwardKL

Fragmentation of Golgi complex and Golgi autoantigens during apoptosis and necrosis.

DOI：
10.1186/ar422
发表时间：
2002
期刊：
Arthritis research
影响因子：
0
作者：
Nozawa K;Casiano CA;Hamel JC;Molinaro C;Fritzler MJ;Chan EK
通讯作者：
Chan EK

Co-clustering of Golgi complex and other cytoplasmic organelles to crescentic region of half-moon nuclei during apoptosis.

DOI：
10.1016/j.cellbi.2008.10.016
发表时间：
2009-02
期刊：
CELL BIOLOGY INTERNATIONAL
影响因子：
3.9
作者：
Nozawa, Kazuhisa;Fritzler, Marvin J.;Takasaki, Yoshinari;Wood, Malcolm R.;Chan, Edward K. L.
通讯作者：
Chan, Edward K. L.

Identification and characterization of a novel Golgi protein, golgin-67.

新型高尔基体蛋白 golgin-67 的鉴定和表征。