INTESTINAL AND HEPATIC MEMBRANES: FLUIDITY AND FUNCTION

肠膜和肝膜：流动性和功能

• 批准号: 3226906
• 负责人: David Schachter
• 金额: $ 17.58万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-07-01 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3226906
• 关键词: all trans retinol; basolateral membrane; calcium transporting ATPase; cholesterol; electron microscopy; gastrointestinal epithelium; gastrointestinal nutrient absorption; ion transport; laboratory rat; liver cirrhosis; membrane permeability; membrane structure; molecular biology; nutrition related tag; peptic ulcer; steroid biosynthesis; tropical sprue

The overall goal of the research is to characterize the molecular mechanisms which mediate and regulate the functions of specialized plasma membranes of the digestive system of the rat, i.e., enterocyte microvillus and basolateral membranes and hepatocyte plasma membranes. Particular emphasis is on the lipis fluidity and lipid-protein interactions in these organelles. purified membrane preparations are examined by biochemical methods; fluorescence techniques, including fluorescence polarization, phase luorometry and excimer fluoresence; and studies of enzyme and transport functions. The specific aims are to characterize the mechanisms which regulate membrane lipid fluidity and, thereby, function. One category of regulatory mechanism is "metabolic", i.e., involves enzyme-mediated changes in membrane lipid composition. The effects of calium in vitro on hepatocyte plasma membranes, of a starve-prefeed dietary regimen on hepatocyte plasma membranes, and of changes in cholesterol biosynthesis in vivo on intestinal microvillus membranes fall in this category. The effects of calcium may underly its regulatory influence on a number of membrane functions, including hormone-mediated signal-transduction and active transport of sodium and potassium. the starverefeed dietery regimen ameliorates partially the cholestasis due to ethinyl estradiol in the rat. Studies are directed to devise effective dietary modulation of membrane fluidity, both as an experimental tool and as a possible therapeutic modality in cholestatic disorders. Impermeant fluorophores are applied to the estimation of the fluidity of the individual hemileaflets of the membranes. These probes permit selective evaluation of the outer hemi- leaflet fluidity of intact cells and will be used to monitor the leaflets of normal and perturbed cells. Thermotropic transitions are studied by fluorescence techniques and differential scanning calorimetry. Fluidity and lipid composition of these plasma membranes are also examined in reltion to rat age, gender, localization in the intestine and function in digestion, absorption and metabolism. The studies should help elucidate intestinal and hepatic function and disorders such as peptic ulcer, sprue, cirrhosis of the liver and toxic or alcoholic liver disease.

该研究的总体目标是表征分子 介导和调节专业等离子体功能的机制 大鼠消化系统的膜，即肠肠细胞微绒毛 以及基底外侧膜和肝细胞质膜。 特别的 重点是其中的脂质流动性和脂质 - 蛋白质相互作用 细胞器。 通过生化检查纯化的膜制剂 方法;荧光技术，包括荧光极化， 相位液和准分子荧光；以及酶和 运输功能。 具体目的是表征机制 调节膜脂质流动性并因此功能。 一 监管机制的类别是“代谢”，即涉及 酶介导的膜脂质组成的变化。 效果 体外钙在肝细胞质膜上的体外，一种饥饿的饮食 肝细胞质膜的方案，胆固醇变化 体内生物合成在肠道微绒毛膜上的生物合成属于此 类别。 钙的影响可能是其对A的调节作用 膜功能的数量，包括激素介导的 钠和钾的信号转移和主动运输。 这 Starverefeed饮食方案可以部分改善由于 大鼠中的乙醇雌二醇。 研究被指示有效 膜流动性的饮食调节，无论是作为实验工具还是 作为胆固性疾病中可能的治疗方式。 拼凑 荧光团应用于估计的流动性 膜的单个半叶。 这些探针允许选择性 评估完整细胞的外半叶流体的流体，将是 用于监测正常和扰动细胞的传单。 热型 通过荧光技术和差异研究过渡 扫描量热法。 这些等离子体的流动性和脂质组成 还检查了膜与大鼠年龄，性别，本地化的膜检查 肠道，吸收和代谢中的肠道和功能。 这 研究应有助于阐明肠和肝功能和疾病 例如消化性溃疡，泉水，肝脏的肝硬化以及有毒或酒精 肝病。