STUDIES OF HEPATIC RECEPTORS FOR GLYCOPROTEINS

肝糖蛋白受体的研究

• 批准号: 4690019
• 负责人: E ANTHONY JONES
• 金额: --
• 依托单位: NAT INST OF ARTHRITIS, DIABETES, DIGESTIVE & KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4690019
• 关键词: Kupffer's cell; N acetylglucosamine; density gradient ultracentrifugation; fasting; glucose metabolism; liver metabolism; lysozyme; mannose; perfusion; radiotracer; tissue /cell culture; vascular endothelium

The cellular location and carbohydrate specificities of a glycoprotein recognition system on rat hepatic sinusoidal cells have been determined. Purified preparations of endothelial, Kupffer and parenchymal cells have been prepared by in situ collagenase liver perfusion, centrifugation on Percoll gradients and centrifugal elutriation. I125-labeled agalactoorosomucoid (AGOR), an N-acetylglucosamine-terminated glycoprotein, was selectively and specifically taken up in vitro by endothelial cells. Glucose and a glucose-albumin conjugate competitively inhibited this uptake process over a wide range of concentrations. Uptake by cells from fasted rats was enhanced, but uptake by cells from fasted or fed diabetic rats was normal. The in vivo hepatic uptake and catabolism of I125-AGOR were slower in diabetic than normal rats. These findings indicate that 1) the hepatic receptors which recognize N-acetylglucosamine/mannose terminated glycoproteins are located predominantly on endothelial cells, 2) these receptors are glucose sensitive, 3) fasting increases the number of these receptors and 4) diabetes mellitus abolishes this effect of fasting and impairs the function of this receptor in vivo. The results of this study suggest a mechanism for abnormal glycoprotein metabolism in diabetes mellitus. This carbohydrate recognition system may play an important role in the removal of potentially autodestructive glycoprotein lysosomal hydrolases and other glcoprotein enzymes from the circulation under normal physiological conditions and in disease states.

糖蛋白的细胞定位和碳水化合物特性 建立了大鼠肝窦细胞的识别系统。 内皮细胞、枯否细胞和实质细胞的纯化制剂 经原位胶原酶肝脏灌流、离心法制备 Percoll梯度和离心洗脱。I125-标签 无乳糖粘蛋白(AGOR)，一种N-乙酰氨基葡萄糖终止的糖蛋白， 在体外被内皮细胞选择性和特异性地摄取。 葡萄糖和葡萄糖-白蛋白结合物竞争性地抑制这种摄取 在广泛的浓度范围内进行加工。细胞对FASED的摄取 大鼠的摄取增加，但禁食或喂食糖尿病大鼠的细胞摄取 很正常。肝脏对I125-AGOR的摄取和分解代谢较慢 糖尿病大鼠较正常大鼠。这些发现表明：1)肝脏 识别N-乙酰氨基葡萄糖/甘露糖终止的受体 糖蛋白主要位于内皮细胞上，2)这些 受体是葡萄糖敏感的，禁食会增加这些受体的数量 受体和4)糖尿病消除了禁食和 在体内损害这种受体的功能。这项研究的结果 提示糖尿病糖蛋白代谢异常的机制 糖尿病。这种碳水化合物识别系统可能起到重要作用。 在清除潜在的自杀性糖蛋白溶酶体中 正常情况下循环中的水解酶和其他糖蛋白酶 生理状态和疾病状态。