Sex hormones regulate NHE1 functional expression and brain endothelial proteome to control paracellular integrity of the blood endothelial barrier.
Sex hormones regulate NHE1 functional expression and brain endothelial proteome to control paracellular integrity of the blood endothelial barrier.
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DOI：
10.1016/j.brainres.2021.147448
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发表时间：
2021-07-15
期刊：
影响因子：
2.9
通讯作者：
中科院分区：
文献类型：
--
作者：
性激素与许多生理系统的pH调节有关。这些研究的一个一致的因素是钠氢交换器1 （NHE1）。NHE1与上皮屏障处的pH稳态有关。激素波动与血脑屏障(BBB)/血内皮屏障（BEB）完整性破坏的保护和风险有关。然而，很少有研究在性激素调节pH稳态的背景下研究神经系统疾病的血脑屏障/BEB完整性。将生理相关浓度的17-β-雌二醇（E2, 294 pM）、孕酮（P, 100 nM）和睾酮（T,3.12 nM）分别应用于培养的永生化弯曲细胞。3个脑内皮细胞研究BEB。单个性腺激素对细胞外pH （E2）、14c -蔗糖摄取(T)、刺激的细胞旁破坏(P)有优先作用，依赖于功能性NHE1表达，而不影响跨内皮抵抗（TEER）或总蛋白表达。通过全细胞裂解和亚细胞分离实验发现，NHE1的总表达没有改变，但表面膜表达的NHE1生物素化显示E2降低了功能表达。定量蛋白质组学分析显示，17-β-雌二醇和睾酮对bEnd蛋白丰度变化的影响不同。3个内皮细胞与未治疗对照组相比。这些数据表明，性激素循环水平可能通过以下途径独立控制BEB完整性：1)通过NHE1功能表达调节pH稳态；2)修改内皮蛋白组。
Sex hormones have been implicated in pH regulation of numerous physiological systems. One consistent factor of these studies is the sodium-hydrogen exchanger 1 (NHE1). NHE1 has been associated with pH homeostasis at epithelial barriers. Hormone fluctuations have been implicated in protection and risk for breaches in blood brain barrier (BBB)/blood endothelial barrier (BEB) integrity. Few studies, however, have investigated BBB/BEB integrity in neurological disorders in the context of sex-hormone regulation of pH homeostasis. Physiologically relevant concentrations of 17-β-estradiol (E2, 294 pM), progesterone (P, 100 nM), and testosterone (T,3.12 nM) were independently applied to cultured immortalized bEnd.3 brain endothelial cells to study the BEB. Individual gonadal hormones showed preferential effects on extracellular pH (E2), 14C-sucrose uptake (T), stimulated paracellular breaches (P) with dependence on functional NHE1 expression without impacting transendothelial resistance (TEER) or total protein expression. While total NHE1 expression was not changed as determined via whole cell lysate and subcellular fractionation experiment, biotinylation of NHE1 for surface membrane expression showed E2 reduced functional expression. Quantitative proteomic analysis revealed divergent effects of 17-β-estradiol and testosterone on changes in protein abundance in bEnd.3 endothelial cells as compared to untreated controls. These data suggest that circulating levels of sex hormones may independently control BEB integrity by 1) regulating pH homeostasis through NHE1 functional expression and 2) modifying the endothelial proteome.
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DOI：
10.1016/0167-4781(95)00075-r
发表时间：
1995-06-09
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
BLAUROCK, MC;REBOUCAS, NA;IGARASHI, P
通讯作者：
IGARASHI, P
影响因子：
6.3
作者：
Andrew, R. David;Hsieh, Yi-Ting;Brisson, C. Devin
通讯作者：
Brisson, C. Devin
影响因子：
4.8
作者：
Beydoun, Rami;Hamood, Mohamed A.;Kondapalli, Kalyan C.
通讯作者：
Kondapalli, Kalyan C.
影响因子：
5.6
作者：
Chien, Eileen Jea;Liao, Ching-Fong;Hsu, Ming-Ta
通讯作者：
Hsu, Ming-Ta
影响因子：
2.9
作者：
Castaneda-Corral, Gabriela;Rocha-Gonzalez, Hector I.;Granados-Soto, Vinicio
通讯作者：
Granados-Soto, Vinicio