NRAMP--MYCOBACTERIAL RESISTANCE, MRNA STABILITY AND IRON

NRAMP--分枝杆菌耐药性、mRNA 稳定性和铁

• 批准号: 2540425
• 负责人: BRUCE S ZWILLING
• 金额: $ 25.55万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2540425
• 关键词: Mycobacterium; bactericidal immunity; cell line; chemical stability; disease /disorder proneness /risk; genetically modified animals; immunogenetics; intracellular transport; iron metabolism; laboratory mouse; leukocyte activation /transformation; macrophage; messenger RNA; protein transport; transfection; transport proteins

DESCRIPTION Innate host resistance to infectious agents plays an important role in determining whether infection by pathogenic microorganisms progresses to disease or whether the microorganisms are eliminated. Resistance to the growth of several intracellular pathogens, including Mycobacteria, Salmonella and Leishmania is mediated by the macrophage and is controlled by a gene, now called Nramp1, a natural resistance associated macrophage protein. The gene appears to control the functional capacity of macrophages such that macrophages that express the functional protein appear to be at a more heightened state of activation than are macrophages that do not express a functional protein. The function of the gene product in controlling resistance is not known. Based on nucleotide sequence analysis the deduced protein appears to be a transport protein. The specific aims are to: 1) correlate mycobacterial resistance, using lung and splenic macrophages, with stable expression of mRNA and the intracellular iron with Nramp1 using both congenic and transgenic mice; 2) determine the role of Nramp1Gly169 in transition metal transport; 3) determine the role of intracellular iron and Nramp1 in mRNA stability and protein synthesis using cell lines transfected with Nramp1Gly169 and Nramp1Asp169; and 4) determine the mechanism of mRNA stability induced by iron.

描述 宿主对感染因子的先天抗性在以下方面起着重要作用： 确定病原微生物感染是否进展为 疾病或微生物是否被消除。阻力 几种细胞内病原体的生长，包括分枝杆菌， 沙门氏菌和利什曼原虫是由巨噬细胞介导的， 一种基因，现在被称为Nramp 1，一种与巨噬细胞天然抗性相关的基因， 蛋白该基因似乎控制巨噬细胞的功能能力 使得表达功能性蛋白的巨噬细胞似乎处于 比不表达的巨噬细胞更高的激活状态 一种功能性蛋白质基因产物在调控中的作用 阻力未知。根据核苷酸序列分析， 蛋白质似乎是一种转运蛋白。具体目标是：1） 使用肺和脾巨噬细胞将分枝杆菌耐药性与 mRNA和细胞内铁的稳定表达与Nramp 1使用两者 同源和转基因小鼠; 2）确定Nramp 1Gly 169在 过渡金属转运; 3）确定细胞内铁的作用， 使用转染的细胞系研究Nramp 1在mRNA稳定性和蛋白质合成中的作用 与Nramp 1Gly 169和Nramp 1Asp 169的相互作用;以及4）确定mRNA 铁引起的稳定性。