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Estrogen negatively regulates the renal epithelial sodium channel (ENaC) by promoting Derlin-1 expression and AMPK activation.
Experimental & Molecular Medicine ( IF 9.5 ) Pub Date : 2019-05-21 , DOI: 10.1038/s12276-019-0253-z
Xue Zhang 1 , Yamei Ge 1 , Ashfaq-Ahmad-Shah Bukhari 1 , Qian Zhu 1 , Yachen Shen 1 , Min Li 1 , Hui Sun 1 , Dongming Su 2, 3 , Xiubin Liang 1, 3
Experimental & Molecular Medicine ( IF 9.5 ) Pub Date : 2019-05-21 , DOI: 10.1038/s12276-019-0253-z
Xue Zhang 1 , Yamei Ge 1 , Ashfaq-Ahmad-Shah Bukhari 1 , Qian Zhu 1 , Yachen Shen 1 , Min Li 1 , Hui Sun 1 , Dongming Su 2, 3 , Xiubin Liang 1, 3
Affiliation
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The main functions of the epithelial sodium channel (ENaC) in the kidney distal nephron are mediation of sodium and water balance and stabilization of blood pressure. Estrogen has important effects on sodium and water balance and on premenopausal blood pressure, but its role in the regulation of ENaC function is not fully understood. Female Sprague-Dawley rats were treated with 17β-estradiol for 6 weeks following bilateral ovariectomy. Plasma estrogen, aldosterone, creatinine, and electrolytes were analyzed, and α-ENaC and derlin-1 protein expression in the kidney was determined by immunohistochemistry and western blotting. The expression levels of α-ENaC, derlin-1, AMPK, and related molecules were also examined by western blotting and real-time PCR in cultured mouse renal collecting duct (mpkCCDc14) epithelial cells following estrogen treatment. Immunofluorescence and coimmunoprecipitation were performed to detect α-ENaC binding with derlin-1 and α-ENaC ubiquitination. The results demonstrated that the loss of estrogen elevated systolic blood pressure in ovariectomized (OVX) rats. OVX rat kidneys showed increased α-ENaC expression but decreased derlin-1 expression. In contrast, estrogen treatment decreased α-ENaC expression but increased derlin-1 expression in mpkCCDc14 cells. Moreover, estrogen induced α-ENaC ubiquitination by promoting the interaction of α-ENaC with derlin-1 and evoked phosphorylation of AMPK in mpkCCDc14 cells. Our study indicates that estrogen reduces ENaC expression and blood pressure in OVX rats through derlin-1 upregulation and AMPK activation.
中文翻译：
雌激素通过促进Derlin-1表达和AMPK激活来负调节肾上皮钠通道（ENaC）。
肾远端肾单位中的上皮钠通道（ENaC）的主要功能是调节钠和水的平衡并稳定血压。雌激素对钠和水的平衡以及绝经前的血压有重要影响，但其在ENaC功能调节中的作用尚不完全清楚。在双侧卵巢切除术后，雌性Sprague-Dawley大鼠用17β-雌二醇治疗6周。分析血浆雌激素，醛固酮，肌酐和电解质，并通过免疫组织化学和蛋白质印迹法测定肾脏中的α-ENaC和derlin-1蛋白表达。雌激素处理后，在培养的小鼠肾收集管（mpkCCDc14）上皮细胞中也通过蛋白质印迹和实时PCR检测了α-ENaC，derlin-1，AMPK和相关分子的表达水平。进行免疫荧光和共免疫沉淀以检测与derlin-1和α-ENaC泛素化的α-ENaC结合。结果表明，卵巢切除（OVX）大鼠体内雌激素的丢失使收缩压升高。OVX大鼠肾脏显示α-ENaC表达增加，但derlin-1表达减少。相反，雌激素处理可降低mpkCCDc14细胞中α-ENaC的表达，但增加derlin-1的表达。此外，雌激素通过促进α-ENaC与derlin-1的相互作用以及在mpkCCDc14细胞中引起AMPK的磷酸化来诱导α-ENaC泛素化。我们的研究表明，雌激素可通过derlin-1上调和AMPK激活来降低OVX大鼠的ENaC表达和血压。
更新日期：2019-05-21
中文翻译：
雌激素通过促进Derlin-1表达和AMPK激活来负调节肾上皮钠通道（ENaC）。
肾远端肾单位中的上皮钠通道（ENaC）的主要功能是调节钠和水的平衡并稳定血压。雌激素对钠和水的平衡以及绝经前的血压有重要影响，但其在ENaC功能调节中的作用尚不完全清楚。在双侧卵巢切除术后，雌性Sprague-Dawley大鼠用17β-雌二醇治疗6周。分析血浆雌激素，醛固酮，肌酐和电解质，并通过免疫组织化学和蛋白质印迹法测定肾脏中的α-ENaC和derlin-1蛋白表达。雌激素处理后，在培养的小鼠肾收集管（mpkCCDc14）上皮细胞中也通过蛋白质印迹和实时PCR检测了α-ENaC，derlin-1，AMPK和相关分子的表达水平。进行免疫荧光和共免疫沉淀以检测与derlin-1和α-ENaC泛素化的α-ENaC结合。结果表明，卵巢切除（OVX）大鼠体内雌激素的丢失使收缩压升高。OVX大鼠肾脏显示α-ENaC表达增加，但derlin-1表达减少。相反，雌激素处理可降低mpkCCDc14细胞中α-ENaC的表达，但增加derlin-1的表达。此外，雌激素通过促进α-ENaC与derlin-1的相互作用以及在mpkCCDc14细胞中引起AMPK的磷酸化来诱导α-ENaC泛素化。我们的研究表明，雌激素可通过derlin-1上调和AMPK激活来降低OVX大鼠的ENaC表达和血压。
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