Exploring mechanisms of protein influence on calcium oxalate kidney stone formation.
Exploring mechanisms of protein influence on calcium oxalate kidney stone formation.
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DOI：
10.1007/s00240-021-01247-5
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发表时间：
2021-08
期刊：
影响因子：
3.1
通讯作者：
Wesson JA
中科院分区：
文献类型：
--
作者：
Berger GK;Eisenhauer J;Vallejos A;Hoffmann B;Wesson JA
一水草酸钙（COM）晶体是大多数肾结石的主要成分，但结石基质中的尿蛋白被认为是这些晶体形成结石的关键元素。最近的数据表明，在结石基质中出现了数百种蛋白质，但没有解释包含如此多的蛋白质。我们提出了一个结石形成模型与蛋白质刺激COM聚集的基础上聚阴离子-聚阳离子聚集，这是支持发现，基质是高度富集在强阴离子和强阳离子蛋白质。许多其他蛋白质由于在水中的溶解度有限或电荷效应而可能被吸引到此类聚集体中。在多聚精氨酸（pR）诱导的尿蛋白聚集体和COM结石基质中发现类似的蛋白富集将支持这一假设。通过超渗滤从6名健康成人的随机尿液样品中获得纯化蛋白（PP）。通过向两种浓度的PP溶液中加入pR诱导蛋白质聚集; 0.25和0.5 μg pR /μg PP。将每个级分和原始PP混合物的样品冻干并通过串联质谱法进行分析。聚集诱导的PR除了PP样品收集的蛋白质混合物，模拟COM矩阵中观察到的蛋白质分布，支持我们的假设。当某些丰富的阴离子蛋白质在COM结石基质中的丰度降低时，它们优先加入pR聚集体的明显不一致行为表明该模型被过度驱动而聚集。在低pR添加下，白蛋白聚集体偏好的逆转支持这一解释。
Calcium oxalate monohydrate (COM) crystals are the primary constituent of most kidney stones, but urine proteins in stone matrix are believed to be critical elements for stone formation from these crystals. Recent data have shown that hundreds of proteins appear in the stone matrix with no explanation for inclusion of so many proteins. We have proposed a stone formation model with protein stimulated COM aggregation based on polyanion-polycation aggregation, which is supported by finding that matrix is highly enriched in strongly anionic and strongly cationic proteins. Many other proteins may be drawn to such aggregates due to their limited solubility in water or charge effects. Finding similar protein enrichment in both polyarginine (pR) induced aggregates of urine proteins and COM stone matrix would support this hypothesis. Purified proteins (PP) were obtained from random urine samples of six healthy adults by ultradiafiltration. Protein aggregation was induced by adding pR to PP solutions at two concentrations; 0.25 and 0.5 μg pR /μg of PP. Samples of each fraction and the original PP mixture were lyophilized and analyzed by tandem mass spectrometry. Aggregates induced by pR addition to PP samples collected a protein mixture that mimicked the protein distribution observed in COM matrix, supporting our hypothesis. The apparently discordant behavior of certain abundant anionic proteins preferentially joining the pR aggregate, when they had demonstrated reduced abundance in COM stone matrix, suggests that this model was overdriven to aggregate. The reversal of aggregate preference of albumin at low pR addition supports this interpretation.
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影响因子：
3.1
作者：
Evan AP;Worcester EM;Coe FL;Williams J Jr;Lingeman JE
通讯作者：
Lingeman JE
Biopython：用于计算分子生物学和生物信息学的免费 Python 工具。
DOI：
10.1093/bioinformatics/btp163
发表时间：
2009-06-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Cock PJ;Antao T;Chang JT;Chapman BA;Cox CJ;Dalke A;Friedberg I;Hamelryck T;Kauff F;Wilczynski B;de Hoon MJ
通讯作者：
de Hoon MJ
DOI：
10.1152/ajprenal.00134.2008
发表时间：
2008-10-01
影响因子：
4.2
作者：
Merchant, Michael L.;Cummins, Timothy D.;Lederer, Eleanor D.
通讯作者：
Lederer, Eleanor D.
影响因子：
--
作者：
Wesson, JA;Ganne, V;Kleinman, JG
通讯作者：
Kleinman, JG
影响因子：
3.1
作者：
Wang, Zhu;Zhang, Jian-wen;Liang, Hui
通讯作者：
Liang, Hui