Caffeine prevents kidney stone formation by translocation of apical surface annexin A1 crystal-binding protein into cytoplasm: In vitro evidence.
Caffeine prevents kidney stone formation by translocation of apical surface annexin A1 crystal-binding protein into cytoplasm: In vitro evidence.
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DOI：
10.1038/srep38536
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发表时间：
2016-12-07
影响因子：
4.6
通讯作者：
Thongboonkerd V
中科院分区：
文献类型：
--
作者：
Peerapen P;Thongboonkerd V
最近的三大队列研究表明，饮用含咖啡因的饮料与患肾结石疾病的风险较低相关。然而，其保护机制仍不清楚，以前也没有研究过。因此，我们通过结晶、晶体生长、细胞-晶体黏附、Western blotting和免疫荧光分析，评估了咖啡因(1 μM-10 mm)对一水草酸钙(COM)肾结石形成的保护作用。结果表明，咖啡因减少了晶体的数量，但增加了晶体的尺寸，导致晶体质量不变，与不受咖啡因影响的晶体生长一致。然而，咖啡因以剂量依赖的方式显著降低MDCK肾小管细胞的晶体结合能力。Western blotting和免疫荧光研究显示，咖啡因处理的细胞顶端表面膜联蛋白A1的表达水平显著降低，其转位进入细胞质，而其他COM晶体结合蛋白(膜联蛋白A2、α-烯醇化酶、热休克蛋白70和热休克蛋白90)的表达无明显变化。此外，咖啡因降低了细胞内[Ca~(2+)]，但增加了[Ca~(2+)]分泌指数。综上所述，我们的研究结果表明，咖啡因对肾结石形成的保护机制是通过将膜联蛋白A1从肾尖表面移位到细胞质中，降低肾小管上皮细胞的晶体结合能力来实现的。
Recent large 3 cohorts have shown that caffeinated beverage consumption was associated with lower risk of kidney stone disease. However, its protective mechanisms remained unknown and had not been previously investigated. We thus evaluated protective effects of caffeine (1 μM–10 mM) on calcium oxalate monohydrate (COM) kidney stone formation, using crystallization, crystal growth, cell-crystal adhesion, Western blotting, and immunofluorescence assays. The results showed that caffeine reduced crystal number but, on the other hand, increased crystal size, resulting in unchanged crystal mass, consistent with crystal growth that was not affected by caffeine. However, caffeine significantly decreased crystal-binding capacity of MDCK renal tubular cells in a dose-dependent manner. Western blotting and immunofluorescence study of COM crystal-binding proteins revealed significantly decreased level of annexin A1 on apical surface and its translocation into cytoplasm of the caffeine-treated cells, but no significant changes in other COM crystal-binding proteins (annexin A2, α-enolase, HSP70, and HSP90) were observed. Moreover, caffeine decreased intracellular [Ca2+] but increased [Ca2+] secretory index. Taken together, our findings showed an in vitro evidence of the protective mechanism of caffeine against kidney stone formation via translocation of annexin A1 from apical surface into cytoplasm to reduce the crystal-binding capacity of renal tubular epithelial cells.
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影响因子：
1.3
作者：
Echeverri D;Montes FR;Cabrera M;Galán A;Prieto A
通讯作者：
Prieto A
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