SAA LIPOPROTEIN FAMILY--FUNCTION & ROLE IN AMYLOIDOSIS

SAA 脂蛋白家族--功能

• 批准号: 3357155
• 负责人: EARL P BENDITT
• 金额: $ 18.34万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1993-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3357155
• 关键词: amyloid proteins; amyloidosis; antibody; apolipoproteins; binding proteins; cell type; cellular pathology; cholesterol; disease /disorder classification; disease /disorder model; genetic manipulation; high density lipoproteins; immunochemistry; laboratory mouse; laboratory rabbit; lipid transport; messenger RNA; molecular cloning; molecular pathology; nucleic acid hybridization; protein biosynthesis; receptor; tissue /cell culture

Amyloidosis comprises a group of disorders characterized by the extracellular accumulation of protein fibrils. The distribution of such fibrils in subendothelial locations of affected organs and vessels can lead to the eventual impairment of vital organ functions. Analysis of the major polypeptide constituents of amyloid deposits reveals distinct classes derived from normal plasma constituents. Serum amyloid A (apoSAA) is a unique family of plasma HDL apoproteins that are precursors of the amyloid A fibril protein of AA type amyloidosis. Nothing is known about the function(s) of the apoSAA's and little is known concerning their role in the development of amyloidosis. The major aims of this project are 1) to elucidate the function(s) of the SAA apoprotein family, 2) to investigate the mechanisms of the pathogenesis of the AA variety of amyloidosis and 3) to ask whether and, if so, in what ways the principles underlying amyloidogenesis of the AA type are relevant to other types of amyloidosis. The mouse model system will be used to continue our investigations. We will identify the cell types responsible for synthesis of SAA1, SAA2 and SAA3 mRNA. We will identify the SAA3 apoprotein and examine the tissue interactions and fate of the three SAA apoproteins. Fibroblasts, macrophages, endothelial cells, smooth muscle cells, and adrenal gland will be examined for the presence of apoSAA HDL-specific receptors. If the apoSAA HDL receptor is identified, we will ascertain whether it is distinct from the HDL receptor, whether it is regulated in response to injury or inflammatory conditions, what cell types possess it, and whether its levels are elevated in amyloidotic tissues. The possibility that SAA alters cholesterol transport activities of HDL will be tested. The role of apoSAA-HDL interaction with cells or matrix components will be explored in regard to pathogenesis of AA type amyloidosis.

淀粉样变性包括一组以以下特征为特征的疾病： 细胞外蛋白质原纤维的积累。 的分布 这些原纤维位于受影响器官的内皮下位置， 血管最终可能导致重要器官受损 功能。 主要多肽成分分析 淀粉样蛋白沉积物揭示了源自正常淀粉样蛋白的不同类别 血浆成分。 血清淀粉样蛋白 A (apoSAA) 是血浆 HDL 的一个独特家族 脱辅基蛋白是淀粉样蛋白A原纤维蛋白的前体 AA型淀粉样变性。 关于其功能一无所知 apoSAA 的作用却鲜为人知 淀粉样变性的发展。 该项目的主要目标是 1) 阐明 SAA 脱辅基蛋白家族的功能，2) 探讨AA品种的发病机制 3) 询问淀粉样变性是否以及如果是的话，通过什么方式 AA 型淀粉样蛋白形成的原理是相关的 其他类型的淀粉样变性。 小鼠模型系统将是 用于继续我们的调查。 我们将识别细胞 负责合成 SAA1、SAA2 和 SAA3 mRNA 的类型。 我们将鉴定 SAA3 脱辅基蛋白并检查组织 三种 SAA 脱辅基蛋白的相互作用和命运。 成纤维细胞、巨噬细胞、内皮细胞、平滑肌细胞、 并检查肾上腺是否存在 apoSAA HDL 特异性受体。 如果 apoSAA HDL 受体是 确定后，我们将确定它是否与 HDL 不同 受体，无论是响应损伤还是调节 炎症状况、哪些细胞类型具有这种状况以及是否 它的水平在淀粉样组织中升高。 的可能性是 SAA 改变 HDL 的胆固醇转运活性将被测试。 apoSAA-HDL 与细胞或基质相互作用的作用 将探讨 AA 型发病机制的组成部分 淀粉样变性。