HUMAN HEART FATTY ACID BINDING PROTEINS

人心脏脂肪酸结合蛋白

• 批准号: 3353395
• 负责人: ROBERT F TROXLER
• 金额: $ 15.75万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3353395
• 关键词: DNA binding protein; adipose tissue; antiserum; binding proteins; complementary DNA; enzyme linked immunosorbent assay; fatty acid metabolism; fatty acid transport; gene expression; genetic enhancer element; heart cell; heart metabolism; human tissue; laboratory rabbit; laboratory rat; liver cells; membrane model; membrane proteins; molecular cloning; molecular pathology; peptides; protein metabolism; protein sequence; protein structure function

Fatty acid binding proteins (FABPS) are members of a superfamily of abundant, low Mr (12-14 kd) hydrophobic ligand binding proteins widely distributed in mammalian tissues. These proteins are believed to be responsible for the intracellular transport of fatty acids, and because they comprise up to 5% of heart cytosolic protein, they have been implicated in, protecting cell and organellar membranes from the detergent-like effects of long chain fatty acids and their metabolites which accumulate in ischemia. FABPs are expressed in an interesting tissue specific manner. Heart FABP (M-FABP) is expressed in heart, liver FABP (L-FABP) is expressed in liver and intestine, intestine FABP (I-FABP) is expressed only in intestine and kidney FABP (K-FABP),is expressed only in kidney. Nothing is known about the tissue specific factors which regulate expression of the genes for FABP. Recently, isoforms of a 40 kd plasma membrane fatty acid binding protein have been isolated from heart, liver, intestine and adipose tissue. These proteins are thought to mediate saturable binding and uptake of fatty acids into cells. The molecular basis for the differences between these 40 kd plasma membrane FABPs is not known, although we have recently determined a portion of the primary structure of the heart plasma membrane FABP, providing the first structural information available on any of these proteins. The specific aims of this project are to: (1) investigate the molecular basis tissue specific expression of the gene for M-FABP by identifying elements in the 5' flanking region of this gene which bind nuclear proteins, (2) isolate the nuclear protein factors which regulate M-FABP gene expression in heart, and (3) characterize the 40 kd plasma membrane FABPs from heart and liver, compare these proteins in peptide mapping and sequencing studies, clone and sequence the heart 40 kd plasma membrane FABP cDNA and investigate the functional properties of this protein in a model membrane system.

脂肪酸结合蛋白（FABP）是一个超家族的成员 丰富的低MR（12-14 kd）疏水配体结合蛋白广泛 分布在哺乳动物组织中。这些蛋白质被认为是 负责脂肪酸的细胞内转运，因为 它们最多占心脏胞质蛋白的5％，它们已经 与保护细胞和细胞器膜有关 长链脂肪酸及其代谢产物的清洁剂样作用 积累在缺血中。 Fabps在有趣的组织中表达 具体方式。心脏Fabp（M-FABP）以心脏，肝脏Fabp表示 （L-FABP）用肝脏和肠道表达 仅在肠和肾脏fabp（k-fabp）中表达，仅在 肾。关于调节的组织特定因素一无所知 FABP基因的表达。最近，40 kD等离子体的同工型 膜脂肪酸结合蛋白已从心脏，肝脏中分离出来 肠道和脂肪组织。这些蛋白质被认为是介导的 可饱和的结合和脂肪酸摄入到细胞中。分子基础 对于这40 kD质膜fabps的差异尚不清楚， 尽管我们最近确定了主要结构的一部分 心脏质膜FABP，提供第一个结构信息 可在任何这些蛋白质上使用。 该项目的具体目的是：（1）研究分子 通过鉴定基因的基因基因的基因表达 该基因结合核的5'侧翼区域的元素 蛋白质，（2）隔离调节M-FABP的核蛋白质因子 心脏中的基因表达，（3）表征40 kD的质膜 从心脏和肝脏中的Fabps，在肽映射中比较这些蛋白质 测序研究，克隆和序列心脏40 kD质膜FABP cDNA并研究该蛋白在模型中的功能特性 膜系统。