Fournier J G, Escaig-Haye F, Billette de Villemeur T, Robain O, Lasmézas C I, Deslys J P, Dormont D, Brown P
U 153 INSERM, Institut de Myologie, Hôpital Pitié-Salpêtrière, 47 Bd de l'Hôpital, F-75651 Paris cedex 13, France.
Cell Tissue Res. 1998 Apr;292(1):77-84. doi: 10.1007/s004410051036.
In transmissible spongiform encephalopathies (TSE), such as scrapie in animals and Creutzfeldt-Jakob disease in humans, the central event is the conversion of a host-encoded amyloidogenic protein (PrPc) into an abnormal isoform (PrPsc) that accumulates as amyloid in TSE brain. PrPc is a membrane sialoglycoprotein synthesized in the central nervous system and elsewhere. We have examined the ultrastructural localization of PrPc in numerous hamster and some human extracerebral tissues, by means of a post-embedding electron-microscopic method combined with immunogold labeling. In stomach, intestine, lung, and kidney from hamsters, and in stomach, kidney, and spleen from humans, immunogold labeling specific for PrPc is observed on various cellular substructures related to secretory pathways: Golgi apparatus, secretory globules, and plasma membrane. In mucous epithelial cells of stomach and intestine, PrPc appears to be concentrated in secretory globules, suggesting a role for PrPc in the secretory function of the digestive tract. The secretory aspect of PrPc may be a key to understanding the physiopathological mechanisms underlying TSE.
在传染性海绵状脑病（TSE）中，如动物的羊瘙痒症和人类的克雅氏病，核心事件是宿主编码的淀粉样蛋白生成蛋白（PrPc）转化为异常异构体（PrPsc），后者在TSE脑内以淀粉样蛋白形式积聚。PrPc是一种在中枢神经系统和其他部位合成的膜唾液糖蛋白。我们通过包埋后电子显微镜方法结合免疫金标记，研究了PrPc在众多仓鼠和一些人类脑外组织中的超微结构定位。在仓鼠的胃、肠、肺和肾以及人类的胃、肾和脾中，在与分泌途径相关的各种细胞亚结构上观察到了对PrPc具有特异性的免疫金标记：高尔基体、分泌小体和质膜。在胃和肠的黏液上皮细胞中，PrPc似乎集中在分泌小体中，这表明PrPc在消化道的分泌功能中发挥作用。PrPc的分泌特性可能是理解TSE潜在生理病理机制的关键。
