Webber Dawn, Chauvet Magali C, Ryall Rosemary L
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch 7701, South Africa.
Urol Res. 2005 Aug;33(4):273-84. doi: 10.1007/s00240-005-0471-9. Epub 2005 May 5.
Crystal adherence to the renal epithelium is widely regarded as a probable mechanism of stone formation. Intracrystalline proteins may provide access to the core of urinary crystals and thereby facilitate the dismantling of these crystals after their attachment to and phagocytosis by renal epithelial cells. The present study investigated the role of proteolysis and limited dissolution of urinary calcium oxalate (CaOx) crystals in South Africa's white and black populations with a view to understanding the remarkably low stone incidence in the black population compared with the whites. CaOx crystals were precipitated from filtered urine or ultrafiltered urine dosed with an intracrystalline protein, urinary prothrombin fragment 1 (UPTF1), isolated from white and black subjects. The crystals were fractured and subjected to proteolysis and/or limited dissolution before examination using field emission scanning electron microscopy (FESEM). FESEM data showed that CaOx crystals from white and black subjects were eroded by treatment with proteases. Cathepsin D caused the most significant crystal erosion, and more noticeable degradation of CaOx monohydrate (COM) crystals compared to CaOx dihydrate (COD). Limited dissolution studies showed the unique ultrastructures and fragmentation processes of COM and COD crystals. COM crystals appeared to be more susceptible to degradation and dissolution than CODs. Since COMs are predominant in blacks, compared with COD crystals from whites, it is speculated that the lower stone rate amongst South African blacks might be attributed partly to their more efficient destruction of retained COM crystals.
晶体附着于肾上皮细胞被广泛认为是结石形成的一种可能机制。晶体内蛋白质可能为进入尿结晶核心提供途径,从而在尿结晶附着于肾上皮细胞并被其吞噬后促进这些结晶的分解。本研究调查了南非白人和黑人人群中草酸钙(CaOx)晶体的蛋白水解和有限溶解作用,旨在了解与白人相比黑人中结石发病率极低的原因。从白人和黑人受试者中分离出的晶体内蛋白质——尿凝血酶原片段1(UPTF1),加入到过滤尿液或超滤尿液中,使CaOx晶体沉淀。在使用场发射扫描电子显微镜(FESEM)检查之前,将晶体破碎并进行蛋白水解和/或有限溶解。FESEM数据显示,白人和黑人受试者的CaOx晶体经蛋白酶处理后被侵蚀。组织蛋白酶D引起的晶体侵蚀最为显著,与二水草酸钙(COD)相比,对一水草酸钙(COM)晶体的降解更明显。有限溶解研究显示了COM和COD晶体独特的超微结构和破碎过程。COM晶体似乎比COD晶体更容易降解和溶解。由于与白人的COD晶体相比,COM在黑人中占主导地位,推测南非黑人中较低的结石发病率可能部分归因于他们对残留COM晶体更有效的破坏。