Haltia A, Solin M L, Jalanko H, Holmberg C, Miettinen A, Holthöfer H
Department of Bacteriology and Immunology, University of Helsinki, Finland.
Histochem J. 1996 Oct;28(10):681-7. doi: 10.1007/BF02409005.
Congenital nephrotic syndrome of the Finnish type is a recessively inherited renal disease with glomerular deposits of the disialoganglioside O-acetyl-GD3. Sphingolipid activator proteins (saposins) stimulate the degradation of glycosphingolipids by lysosomal enzymes, and defects in saposins cause accumulation of substrate lipids in the affected tissues in lysosomal storage disease. Here we report a study of the role of saposins in the accumulation of O-acetyl-GD3 in kidneys of congenital nephrotic syndrome patients. At the mRNA level, the expression of saposin precursor in diseased kidneys appeared normal, and the nucleotide sequence analysis of cDNA clones did not reveal abnormalities in the prosaposin gene. Immunohistologically, saposins were localized mainly to the epithelial cells of the distal renal tubules or to the parietal epithelial cells of glomeruli. In the nephrotic syndrome kidneys, the staining pattern was highly granular and appeared mostly in the apical part of the epithelial lining, unlike the control kidneys. These results show that a major site of ganglioside metabolism is located in the distal nephron. Furthermore, these results suggest that saposins are not directly involved in the metabolism of the terminal sialic acids of disialogangliosides in the nephrotic syndrome kidneys.
芬兰型先天性肾病综合征是一种隐性遗传性肾脏疾病，其肾小球中有双唾液酸神经节苷脂O - 乙酰 - GD3沉积。鞘脂激活蛋白（鞘脂激活蛋白）刺激溶酶体酶对糖鞘脂的降解，鞘脂激活蛋白缺陷会导致溶酶体贮积病中受影响组织中底物脂质的蓄积。在此，我们报告一项关于鞘脂激活蛋白在先天性肾病综合征患者肾脏中O - 乙酰 - GD3蓄积作用的研究。在mRNA水平，患病肾脏中鞘脂激活蛋白前体的表达看似正常，cDNA克隆的核苷酸序列分析未揭示鞘脂原蛋白基因存在异常。免疫组织化学显示，鞘脂激活蛋白主要定位于远端肾小管的上皮细胞或肾小球的壁层上皮细胞。在肾病综合征肾脏中，染色模式呈高度颗粒状，且大多出现在上皮内衬的顶端部分，这与对照肾脏不同。这些结果表明神经节苷脂代谢的主要部位位于远端肾单位。此外，这些结果提示鞘脂激活蛋白不直接参与肾病综合征肾脏中双唾液酸神经节苷脂末端唾液酸的代谢。
