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人钙肾结石蛋白质组。

Proteome of human calcium kidney stones.

机构信息

Department of Urology, University of Minnesota, Minneapolis, Minnesota, USA.

出版信息

Urology. 2010 Oct;76(4):1017.e13-20. doi: 10.1016/j.urology.2010.05.005. Epub 2010 Aug 14.

DOI:10.1016/j.urology.2010.05.005
PMID:20709378
Abstract

OBJECTIVES

Idiopathic calcium oxalate (CaOx) stones are believed to develop attached to papillary subepithelial deposits called Randall's plaques. Calcium phosphate (CaP) stones, conversely, are thought to arise within the inner medullary collecting ducts, enlarging and damaging surround tubular structures as they expand. If this is true, we theorize that differences will be seen within the organic portion (matrix) of CaOx stones compared with CaP stones using a mass spectroscopy (MS) approach.

METHODS

From a cohort of 47 powdered stones, 25 calculi (13 CaOx, 12 CaP) were confirmed to contain a dominant mineral content of >80% by powder x-ray diffraction. Matrix proteins were then extracted, purified, and digested. Peptide tandem MS data were acquired, and spectra were searched against a large human protein database to identify protein matches.

RESULTS

No significant differences were seen between pattern profiles of CaOx and CaP stones. However, variations in protein expression patterns were seen within individual CaOx (monohydrate and dihydrate) and CaP (apatite and brushite) mineral subtypes, suggesting a relationship between crystal-surface binding properties and matrix composition. Both groups contain a large number of inflammatory proteins and a catalog of common proteins is included.

CONCLUSIONS

Calcium kidney stone matrix contains hundreds of proteins and is predominated by proteins associated with inflammatory response. Many of the same proteins were identified in both CaOx and CaP stones, suggesting inflammation as a unifying origin or a common secondary role in calcium stone pathogenesis.

摘要

目的

草酸钙(CaOx)结石被认为是附着在称为 Randall 斑块的乳头下上皮沉积物上形成的。相反,磷酸钙(CaP)结石被认为是在内髓集合管内形成的,随着结石的扩大,会损害周围的管状结构。如果这是真的,我们推测使用质谱(MS)方法,在 CaOx 结石与 CaP 结石的有机部分(基质)中会看到差异。

方法

从 47 个粉末结石的队列中,通过粉末 X 射线衍射证实 25 个结石(13 个 CaOx,12 个 CaP)的主要矿物质含量>80%。然后提取、纯化和消化基质蛋白。获得肽串联 MS 数据,并将其与大型人类蛋白质数据库进行搜索以鉴定蛋白质匹配物。

结果

CaOx 和 CaP 结石的图案谱之间没有明显差异。然而,在个体 CaOx(一水合物和二水合物)和 CaP(磷灰石和水合磷酸氢钙)矿物质亚型中观察到蛋白质表达模式的变化,这表明晶体表面结合特性和基质组成之间存在关系。这两组都含有大量的炎症蛋白,并包含一个常见蛋白目录。

结论

肾结石基质含有数百种蛋白质,主要由与炎症反应相关的蛋白质组成。在 CaOx 和 CaP 结石中都鉴定出许多相同的蛋白质,这表明炎症是钙结石发病机制的一个统一起源或共同的次要作用。

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