How elevated oxalate can promote kidney stone disease: changes at the surface and in the cytosol of renal cells that promote crystal adherence and growth.
How elevated oxalate can promote kidney stone disease: changes at the surface and in the cytosol of renal cells that promote crystal adherence and growth.
复制标题
DOI：
10.2741/1265
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
C. Scheid;Lu-Cheng Cao;T. Honeyman;J. Jonassen
中科院分区：
文献类型：
--
作者：
C. Scheid;Lu-Cheng Cao;T. Honeyman;J. Jonassen
本综述评估了草酸盐诱导的肾细胞功能改变可能促进结石病的机制，重点关注 1) 促进新生晶体附着的膜表面特性的变化，以及 2) 改变晶体成核、团聚和生长动力学的尿大分子表达/分泌的变化。强调了肾细胞损伤在促进这些反应中的一般作用以及尿草酸盐在产生损伤中的具体作用，并讨论了导致观察到的细胞表面特性以及肾细胞活力和生长变化的信号传导途径。特别关注草酸诱导的胞质磷脂酶 A2 激活与基因表达变化以及涉及神经酰胺的第二条信号通路激活之间的联系。脂质信号、花生四烯酸、溶血磷脂酰胆碱和神经酰胺对线粒体功能的影响被详细考虑，因为草酸盐的许多作用似乎是继发于这些细胞器内活性氧分子产生增加的。这些研究以及各种其他体外和体内研究的数据被用来构建一个模型，该模型阐明了尿草酸盐水平增加导致肾结石形成增加的可能机制。需要进一步的研究来评估该模型各个方面的有效性，并确定对抗结石形成个体的这些反应的有效策略。
The present review assesses the mechanisms by which oxalate-induced alterations in renal cell function may promote stone disease focusing on 1) changes in membrane surface properties that promote the attachment of nascent crystals and 2) changes in the expression/secretion of urinary macromolecules that alter the kinetics of crystal nucleation, agglomeration and growth. The general role of renal cellular injury in promoting these responses and the specific role of urinary oxalate in producing injury is emphasized, and the signaling pathways that lead to the observed changes in cell surface properties and in the viability and growth of renal cells are discussed. Particular attention is paid to evidence linking oxalate-induced activation of cytosolic phospholipase A2 to changes in gene expression and to the activation of a second signaling pathway involving ceramide. The effects of the lipid signals, arachidonic acid, lysophosphatidylcholine and ceramide, on mitochondrial function are considered in some detail since many of the actions of oxalate appear to be secondary to increased production of reactive oxygen molecules within these organelles. Data from these studies and from a variety of other studies in vitro and in vivo were used to construct a model that illustrates possible mechanisms by which an increase in urinary oxalate levels leads to an increase in kidney stone formation. Further studies will be required to assess the validity of various aspects of this proposed model and to determine effective strategies for countering these responses in stone-forming individuals.