Selective protein enrichment in calcium oxalate stone matrix: a window to pathogenesis?
Selective protein enrichment in calcium oxalate stone matrix: a window to pathogenesis?
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DOI：
10.1007/s00240-019-01131-3
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发表时间：
2019-12
期刊：
影响因子：
3.1
通讯作者：
Mandel NS
中科院分区：
文献类型：
--
作者：
Wesson JA;Kolbach-Mandel AM;Hoffmann BR;Davis C;Mandel NS
尿蛋白被认为控制草酸钙结石的形成，但超过1000种蛋白质已被报道在结石基质中模糊了它们的相对重要性。与尿液相比，对结石形成至关重要的蛋白质在结石基质中的相对丰度应该增加，因此与先前的尿液蛋白质组数据相比，获得了结石基质的定量蛋白质分布数据。通过晶体溶解从8个结石（草酸钙含量> 90%）中分离基质蛋白，并通过超渗滤（> 10 kDa膜）进一步纯化。使用无标记光谱计数串联质谱法进行蛋白质组学分析，然后进行严格过滤。将平均基质蛋白质组与先前报道的25例草酸钙结石患者随机尿样中观察到的平均尿蛋白质组进行比较。有5种蛋白质在基质中明显富集，占基质蛋白的质量分数> 30%，但仅占尿蛋白的3%。与尿液相比，许多高丰度尿蛋白（如白蛋白和尿调蛋白）以降低的相对丰度存在于基质中，这可能表明基质中存在非选择性包涵体。此外，通过等电点对蛋白质进行分组表明，结石基质蛋白质组高度富集强阴离子（即，骨桥蛋白）和强阳离子（即，组蛋白）蛋白质，其中大多数通常存在于细胞内或核区室中。事实上，高阴离子和高阳离子蛋白质在低浓度下聚集，并且这些聚集体可以诱导晶体聚集，这表明蛋白质聚集可能促进草酸钙结石的形成，而细胞损伤过程与许多细胞内蛋白质的存在有关。
Urine proteins are thought to control calcium oxalate stone formation, but over 1000 proteins have been reported in stone matrix obscuring their relative importance. Proteins critical to stone formation should be present at increased relative abundance in stone matrix compared to urine, so quantitative protein distribution data were obtained for stone matrix compared to prior urine proteome data. Matrix proteins were isolated from eight stones (> 90% calcium oxalate content) by crystal dissolution and further purified by ultradiafiltration (> 10 kDa membrane). Proteomic analyses were performed using label-free spectral counting tandem mass spectrometry, followed by stringent filtering. The average matrix proteome was compared to the average urine proteome observed in random urine samples from 25 calcium oxalate stone formers reported previously. Five proteins were prominently enriched in matrix, accounting for a mass fraction of > 30% of matrix protein, but only 3% of urine protein. Many highly abundant urinary proteins, like albumin and uromodulin, were present in matrix at reduced relative abundance compared to urine, likely indicating non-selective inclusion in matrix. Furthermore, grouping proteins by isoelectric point demonstrated that the stone matrix proteome was highly enriched in both strongly anionic (i.e., osteopontin) and strongly cationic (i.e., histone) proteins, most of which are normally found in intracellular or nuclear compartments. The fact that highly anionic and highly cationic proteins aggregate at low concentrations and these aggregates can induce crystal aggregation suggests that protein aggregation may facilitate calcium oxalate stone formation, while cell injury processes are implicated by the presence of many intracellular proteins.
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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：
Viswanathan, Pragasam;Rimer, Jeffrey D.;Kolbach, Ann M.;Ward, Michael D.;Kleinman, Jack G.;Wesson, Jeffrey A.
通讯作者：
Wesson, Jeffrey A.
影响因子：
--
作者：
Wesson, JA;Ganne, V;Kleinman, JG
通讯作者：
Kleinman, JG
影响因子：
5
作者：
Boonla, Chanchai;Tosukhowong, Piyaratana;Krieglstein, Kerstin
通讯作者：
Krieglstein, Kerstin
影响因子：
2.7
作者：
Chen, Wen-Chi;Lai, Chein-Cheng;Tsai, Fuu-Jen
通讯作者：
Tsai, Fuu-Jen