Santini M T, Masella R, Cantafora A, Peterson S W
Laboratorio di Ultrastrutture, Istituto Superiore di Sanità, Rome, Italy.
Experientia. 1992 Jan 15;48(1):36-9. doi: 10.1007/BF01923602.
We have recently demonstrated, using electron paramagnetic resonance (EPR) spectroscopy, that insulin receptor internalization in response to insulin incubation (down-regulation) in human erythrocytes is accompanied by a transient decrease in membrane order, as measured by the 2T' parallel order parameter. Since membrane lipids play such an important role in receptor internalization, we investigated the possible effects that an alteration of the normally-occurring lipid profile might have on down-regulation and the concomitant transient decrease in membrane order. Consequently, human erythrocytes enriched with cholesterol and erythrocytes from cirrhotic patients were examined, because both of these groups of cells have a higher cholesterol/phospholipid molar ratio (CH/PL) than controls. The 5-nitroxystearate spin label, which inserts into the lipid bilayer of cell membranes, was used to monitor changes in 2T' parallel for a 3-h period at 37 degrees C. We report here that both cholesterol-enriched and cirrhotic erythrocytes do not down-regulate, as demonstrated by binding assays, and that they do not show the typical transient decrease in membrane order observed in controls. The results seem to indicate that a more ordered membrane inhibits internalization of the insulin receptor in erythrocytes, and that an increase in membrane disorder is necessary for insulin receptor down-regulation.
我们最近利用电子顺磁共振（EPR）光谱证明，在人红细胞中，胰岛素孵育后胰岛素受体内化（下调）伴随着膜有序性的短暂降低，这是通过2T'平行有序参数测量的。由于膜脂在受体内化中起着如此重要的作用，我们研究了正常脂质分布的改变可能对下调以及随之而来的膜有序性短暂降低产生的影响。因此，我们检测了富含胆固醇的人红细胞和肝硬化患者的红细胞，因为这两组细胞的胆固醇/磷脂摩尔比（CH/PL）均高于对照组。插入细胞膜脂质双层的5-硝基硬脂酸盐自旋标记物用于在37℃下监测3小时内2T'平行的变化。我们在此报告，结合试验表明，富含胆固醇的红细胞和肝硬化红细胞均未下调，且它们未表现出对照组中观察到的典型膜有序性短暂降低。结果似乎表明，更有序的膜会抑制红细胞中胰岛素受体的内化，而膜无序性的增加对于胰岛素受体下调是必要的。
