calcium collecting ducts diabetes insipidus vasopressin water transport
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摘要

Store-operated calcium entry (SOCE) is the mechanism by which extracellular signals elicit prolonged intracellular calcium elevation to drive changes in fundamental cellular processes. Here, we investigated the role of SOCE in the regulation of renal water reabsorption, using the inbred rat strain SHR-A3 as an animal model with disrupted SOCE. We found that SHR-A3, but not SHR-B2, have a novel truncating mutation in the gene encoding stromal interaction molecule 1 (STIM1), the endoplasmic reticulum calcium (Ca(2+)) sensor that triggers SOCE. Balance studies revealed increased urine volume, hypertonic plasma, polydipsia, and impaired urinary concentrating ability accompanied by elevated circulating arginine vasopressin (AVP) levels in SHR-A3 compared with SHR-B2. Isolated, split-open collecting ducts (CD) from SHR-A3 displayed decreased basal intracellular Ca(2+) levels and a major defect in SOCE. Consequently, AVP failed to induce the sustained intracellular Ca(2+) mobilization that requires SOCE in CD cells from SHR-A3. This effect decreased the abundance of aquaporin 2 and enhanced its intracellular retention, suggesting impaired sensitivity of the CD to AVP in SHR-A3. Stim1 knockdown in cultured mpkCCDc14 cells reduced SOCE and basal intracellular Ca(2+) levels and prevented AVP-induced translocation of aquaporin 2, further suggesting the effects in SHR-A3 result from the expression of truncated STIM1. Overall, these results identify a novel mechanism of nephrogenic diabetes insipidus and uncover a role of SOCE in renal water handling.

译文

储存操纵钙进入 (SOCE) 是细胞外信号引起长期细胞内钙升高以驱动基本细胞过程变化的机制。在这里,我们使用近交系大鼠 SHR-A3 作为破坏的 SOCE 动物模型,研究了 SOCE 在肾脏水重吸收调节中的作用。我们发现 SHR-A3,而不是 SHR-B2,在编码基质相互作用分子 1 (STIM1) 的基因中有一个新的截断突变,内质网钙 (Ca (2)) 触发 SOCE 的传感器。平衡研究显示,与 SHR-A3 相比,SHR-B2 尿量增加、血浆高渗、烦渴和尿液浓缩能力受损,并伴有循环精氨酸加压素 (AVP) 水平升高。从 SHR-A3 分离的、裂开的集合管 (CD) 显示出基底细胞内 Ca (2) 水平下降和 SOCE 的主要缺陷。因此,AVP 未能诱导持续的细胞内 Ca (2) 动员,这需要 SHR-A3 CD 细胞中的 SOCE。这种效应降低了水通道蛋白 2 的丰度,并增强了其细胞内滞留,表明 SHR-A3 中 CD 对 AVP 的敏感性受损。培养的 mpkCCDc14 细胞中的 Stim1 敲除降低了 SOCE 和基础细胞内 Ca (2) 水平,并阻止了 AVP 诱导的水通道蛋白 2 的转位,进一步表明 SHR-A3 的影响是由截短的 Stim1 的表达引起的。总的来说,这些结果确定了肾源性尿崩症的新机制,并揭示了 SOCE 在肾脏水处理中的作用。

Diabetes insipidus

内分泌 肾小管重吸收功能障碍 疾病
概述  :  

尿崩症是一种罕见的疾病,当一个人的肾脏通过异常大量的尿液时,尿液就会稀而无味。在大多数人中,肾脏每天会通过1-2夸脱的尿液,在尿崩症患者中,肾脏每天可以通过3至20夸脱的尿液。由此导致的结果是尿崩症患者可能会需要喝大量的液体。临床分类①中枢性尿崩症当对人的下丘脑或垂体的损害导致正常加压素的产生,储存和释放中断时,就会发生中枢性尿崩症。血管加压素的破坏导致肾脏从体内清除过多的液体,从而导致排尿增加。下丘脑或垂体的损害可能由以下原因引起:手术;感染;肿瘤;头部受伤等。中枢性尿崩症也可能是由产生加

Diabetes  英 /ˌdaɪəˈbiːtiːz/   美 /ˌdaɪəˈbiːtiːz/

释    义   n. 糖尿病;多尿症

同根词   diabetic adj. 糖尿病的,患糖尿病的

               diabetic 糖尿病患者

例    句   It can increase the risk of heart disease, diabetes, and cancer. 它可以增加患心脏病、糖尿病和癌症的风险。

 

insipidus

释    义   n. 尿崩症

例    句   Central diabetes insipidus is usually idiopathic, but can also be caused by head trauma or tumors of the brain. 中枢性尿崩症通常是特发性的,但也能由头部创伤或脑肿瘤引起。

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