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Molecular mechanisms of LPS-induced activation of human monocytes/macrophages: molecular biological studies on functions of mono-ADP-ribosyltransferases ART3 and ART4

LPS诱导人单核细胞/巨噬细胞活化的分子机制：单ADP核糖基转移酶ART3和ART4功能的分子生物学研究

基本信息

批准号：
41407059
负责人：
Professorin Dr. Sunna Hauschildt
金额：
--
依托单位：
Institut für Biologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2007
资助国家：
德国
起止时间：
2006-12-31 至 2011-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/41407059?language=en
关键词：
Molecular mechanisms LPS induced activation

项目摘要

Interaction of human monocytes/macrophages with lipopolysaccharides (LPS), the major outer membrane components of gram-negative bacteria, results in multiple intracellular biochemical modifications that can lead to severe pathophysiological reactions. We have previously shown that LPS induces the mRNA expression of mono-ADP-ribosyltransferase (ART) 3 and 4 and that a 31 kDa protein becomes ADP-ribosylated in response to LPS. ART3/ART4 belong to the family of ARTs which in humans consists of four members (ART1, 3-5). As ARTs are ectoenzymes that catalyze the transfer of ADP-ribose from NAD+ to an acceptor protein thereby modifying its function, ART3/ART4 could well contribute to such functional alterations. So far enzyme activity has only been demonstrated for ART1 and ART5 but not for ART3 and ART4. Molecular biological methods will be used to test whether enzyme activity of ART3/ART4 can be restored and whether ART3/ART4 have gained functional properties that facilitate cell-cell contact by interacting with other surface molecules. As the transcriptional level of ART3/ART4 in activated monocytes/macrophages is extremely low, tissues expressing those mRNA’s at higher levels will be included in the functional studies.

人单核/巨噬细胞与革兰氏阴性菌的主要外膜成分脂多糖（LPS）相互作用，导致多种细胞内生化修饰，可导致严重的病理生理反应。我们之前已经证明，LPS诱导单adp -核糖基转移酶（ART） 3和4的mRNA表达，并且在LPS的响应下，一个31 kDa的蛋白被adp -核糖基化。ART3/ART4属于人类art家族，该家族由四个成员组成（ART1, 3-5）。由于art是催化adp核糖从NAD+转移到受体蛋白从而改变其功能的外切酶，ART3/ART4很可能有助于这种功能改变。到目前为止，仅证实了ART1和ART5的酶活性，而没有证实ART3和ART4的酶活性。分子生物学方法将用于测试ART3/ART4的酶活性是否可以恢复，以及ART3/ART4是否获得了通过与其他表面分子相互作用促进细胞-细胞接触的功能特性。由于活化的单核细胞/巨噬细胞中ART3/ART4的转录水平极低，因此将这些mRNA表达水平较高的组织纳入功能研究。