Andersson G N, Rissler P, Eriksson L C
Department of Pathology, Karolinska Institute, Huddinge University Hospital, Sweden.
Carcinogenesis. 1988 Sep;9(9):1623-8. doi: 10.1093/carcin/9.9.1623.
The asialoglycoprotein (ASGP) receptor, binding and internalizing glycoproteins exposing terminal galactose or N-acetylgalactosamine residues, was compared in normal liver, regenerating liver and liver nodules. The total cellular content of ASGP binding sites was reduced to 50 and 40% in regenerating liver and liver nodules respectively, compared to the level in normal liver. The ASGP receptor was heterogeneously distributed in subcellular fractions, with the highest enrichment (16-fold) found in a low-density membrane fraction (LDMF), enriched in endosomes and Golgi complex membranes. The subcellular distribution pattern was similar in the three different liver tissues, except that the relative enrichment in LDMF was less pronounced in regenerating liver (13-fold) and even less in liver nodules (5-fold). Scatchard analysis of the binding data indicated that the receptor populations in all liver tissues were homogeneous with dissociation constants in the range of 0.12-0.47 nM. The difference in ASGP receptor binding activity was not found to be the result of an increased occupancy with endogenous ligand. In vivo endocytosis of [125I]asialo-orosomucoid ([125I]ASOR) showed a reduction in the amount of internalized ligand in liver nodules, well correlated with the reduced number of binding sites compared to normal liver. However, a slower than normal intracellular metabolism of internalized ligand in the nodules was indicated. Bifunctional cross-linking experiments showed [125I]ASOR--receptor complexes of Mr 250,000, 110,000 and 85,000 in normal and regenerating liver, whereas in liver nodules only the Mr 85,000 was seen. It is concluded that ASGP binding activity is reduced in regenerating liver and in liver nodules. This reduction was manifested predominantly in membranes derived from the Golgi complex, in endocytic vesicles and at the cell surface. The slower than normal rate of decay of the internalized ligand in liver nodules is suggested to be the result of alterations in ligand dissociation and receptor recycling processes. Furthermore, the absence of high molecular cross-linkable [125I]ASOR--receptor complexes in liver nodules may reflect an alteration in receptor oligomerization.
对去唾液酸糖蛋白（ASGP）受体进行了比较，该受体可结合并内化暴露末端半乳糖或N - 乙酰半乳糖胺残基的糖蛋白，比较对象为正常肝脏、再生肝脏和肝结节。与正常肝脏中的水平相比，再生肝脏和肝结节中ASGP结合位点的总细胞含量分别降至50%和40%。ASGP受体在亚细胞组分中呈异质性分布，在富含内体和高尔基体复合膜的低密度膜组分（LDMF）中富集程度最高（16倍）。三种不同肝脏组织中的亚细胞分布模式相似，只是在再生肝脏中LDMF的相对富集程度较低（13倍），在肝结节中更低（5倍）。对结合数据进行Scatchard分析表明，所有肝脏组织中的受体群体均为同质，解离常数在0.12 - 0.47 nM范围内。未发现ASGP受体结合活性的差异是内源性配体占据增加的结果。[125I]去唾液酸血清类黏蛋白（[125I]ASOR）的体内内吞作用显示，肝结节中内化配体的量减少，这与与正常肝脏相比结合位点数量减少密切相关。然而，表明结节中内化配体的细胞内代谢比正常情况慢。双功能交联实验显示，在正常和再生肝脏中，[125I]ASOR - 受体复合物的分子量分别为250,000、110,000和85,000，而在肝结节中仅可见分子量为85,000的复合物。得出的结论是，再生肝脏和肝结节中的ASGP结合活性降低。这种降低主要表现在源自高尔基体复合体、内吞小泡和细胞表面的膜中。肝结节中内化配体衰变速度比正常情况慢，这被认为是配体解离和受体再循环过程改变的结果。此外，肝结节中缺乏高分子量可交联的[125I]ASOR - 受体复合物可能反映了受体寡聚化的改变。
