HUMAN HEART FATTY ACID BINDING PROTEINS

人心脏脂肪酸结合蛋白

• 批准号: 3353393
• 负责人: ROBERT F TROXLER
• 金额: $ 17.97万
• 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 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3353393
• 关键词: antibody; chemical structure function; complementary DNA; covalent bond; enzyme linked immunosorbent assay; fatty acid metabolism; heart metabolism; human subject; human tissue; liposomes; messenger RNA; myocardial infarction; myocardial ischemia /hypoxia; striated muscles

Fatty acid binding proteins (FABPs) comprise a family of abundant, low molecular weight cytosolic proteins found in heart, liver, intestine and other organs. It has been assumed that FABPs function in the intracellular transport of long chain fatty acids and their metabolites. Heart FABPs would be expected to have a particularly important function because fatty acids are a major fuel source for cardiac muscle and because accumulation of amphipathic molecules, such as fatty acids, is believed to cause membrane damage following ischemic injury. The overall goal of this proposal is to understand the role of FABP in human heart. Human heart FABP, which has recently been purified in this laboratory, will be characterized and the complete amino acid sequence determined. FABP from human skeletal muscle will also be purified and its structural relationship to human heart FABP elucidated. Functional studies on both human heart and skeletal muscle FABP will be performed by determining the fatty acid binding characteristics toward five physiologically abundant long chain fatty acids. Binding studies will also be performed on covalently modified proteins to gain insights into the structural features of the fatty acid binding site. Antibodies directed against rat heart FABP have been produced and will be used in an enzyme linked immunosorbant assay to measure FABP levels in normal and ischemic rat heart as well as to determine if FABP levels display a diurnal variation. These studies will be complemented by the use of a cDNA probe for rat heart FABP that will be used to measure FABP mRNA levels in normal and ischemic rat hearts. Antibodies to human heart FABP have also been prepared and have been used to develop an enzyme linked immunosorbant assay for this protein. This assay will be used to measure FABP in serum of patients admitted to the Boston City Hospital Coronary Care Unit to determine if serum levels of FABP can be a useful index of myocardial damage.

脂肪酸结合蛋白（FABPS）包括一个家族 大量的低分子量胞质蛋白在心脏中发现， 肝，肠和其他器官。 已经假定是Fabps 在长链脂肪酸的细胞内运输中的功能 和他们的代谢产物。 心脏晶圆厂有望有一个 特别重要的功能，因为脂肪酸是主要的 心脏肌肉的燃料来源，因为 据信脂肪酸分子（例如脂肪酸）会导致 缺血性损伤后的膜损伤。 该提议的总体目标是了解Fabp的角色 在人类的心中。 Human Heart Fabp，最近 在该实验室中纯化，将被描述为完整 确定的氨基酸序列。 人类骨骼的晶圆厂 肌肉也将被纯化，其结构关系 人心的Fabp阐明了。 对两个人的功能研究 心脏和骨骼肌肉Fabp将通过确定 脂肪酸在生理上的结合特征 丰富的长链脂肪酸。 约束研究也将是 在共价修改的蛋白质上进行，以获取洞察力 脂肪酸结合位点的结构特征。 抗体 针对Rat Heart Fabp已生产，将是 用于链接的免疫吸附测定法以测量FABP 正常和缺血性大鼠心脏的水平以及确定是否 FABP级别显示昼夜变化。 这些研究将是 补充使用cDNA探针对大鼠心脏fabp 这将用于测量正常和 缺血大鼠的心。 人类心脏Fabp的抗体也有 已准备并已用于开发链接的酶 该蛋白质的免疫吸附测定法。 该测定将习惯 测量进入波士顿市的患者血清中的FABP 医院冠状动脉护理部门确定血清水平是否 FABP可能是心肌损伤的有用索引。