Hypertensive sodium-proton exchanger phenotype persists in immortalized lymphoblasts from essential hypertensive patients. A cell culture model for human hypertension.

Hypertensive sodium-proton exchanger phenotype persists in immortalized lymphoblasts from essential hypertensive patients. A cell culture model for human hypertension.
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高血压钠质子交换器表型在原发性高血压患者的永生化淋巴母细胞中持续存在。

DOI:
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发表时间:
1993
影响因子:
15.9
通讯作者:
W. Siffert
W. Siffert
中科院分区:
医学1区
文献类型:
--
作者:
D. Rosskopf;E. Frömter;W. Siffert

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钠-质子交换活性增强是高血压病患者常见的离子转运异常。这一现象的细胞学基础尚未阐明。由于缺乏特定的细胞培养系统,一直无法区分固有的细胞异常和高血压神经体液环境所施加的影响。使用爱泼斯坦-巴尔病毒,我们使来自对照组和表现出增强的钠-质子交换活性的原发性高血压患者的淋巴细胞永生化。用250 nM佛波醇酯12-O-十四酰佛波醇-13-乙酸酯处理细胞10分钟后,用荧光胞液pH指示剂2‘7’-双羧乙基-5,6-羧基荧光素乙酰氧甲酯(BCECF)测定细胞的钠-质子交换活性。高血压患者细胞的钠-质子交换Vmax高于正常血压对照组(129.6±30.0vs.77.1+/-13.2mmolH+/min;P<0.001)。高血压组H+的希尔系数明显低于正常血压组(1.12±-0.12vs.1.50+/-0.14;P<0.0001)。高血压患者细胞系中逆向转运蛋白活性的增强并没有伴随NHE-1mRNA转录水平的相应增加,这与高血压患者中反向转运蛋白的过度表达无关。高血压病患者钠质子交换活性高的细胞增殖速度明显快于正常血压对照组。这些人类细胞系代表了一种研究钠-质子交换和细胞增殖之间相互作用的新模型,并可能为观察到一组高血压患者的离子转运变化提供见解。
An enhancement of sodium-proton exchange activity is a frequently observed ion transport abnormality in essential hypertension. The cellular basis for this has not yet been elucidated. Due to the lack of a specific cell culture system it has been impossible to distinguish between intrinsic cellular abnormalities and influences exerted by the hypertensive neurohumoral milieu. Using Epstein-Barr virus we have immortalized lymphocytes from controls and from patients with essential hypertension that exhibited enhanced sodium-proton exchanger activity. Sodium-proton exchanger activity was determined in cells loaded with the fluorescent cytosolic pH indicator 2'7'-biscarboxyethyl-5,6-carboxyfluorescein acetoxymethylester (BCECF) after pretreatment with 250 nM of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate for 10 min. Cell lines from hypertensive patients displayed higher Vmax values of sodium-proton exchange than those from normotensive controls (129.6 +/- 30.0 vs. 77.1 +/- 13.2 mmol H+/min.; P < 0.001). Hill coefficients for H+ were distinctly lower in hypertension compared to normotension (1.12 +/- 0.12 vs. 1.50 +/- 0.14; P < 0.0001). The enhanced antiporter activity in cell lines from hypertensive patients was not accompanied by a corresponding increase in steady-state NHE-1 mRNA transcript levels, which argues against overexpression of antiporter protein in hypertension. The cells from hypertensive patients with high sodium-proton exchange activity proliferated distinctly faster than those from normotensive controls. These human cell lines represent a novel model to study the mutual interaction between sodium-proton exchange and cell proliferation, and may provide insights into the alterations in ion transport observed in a group of patients with essential hypertension.
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DOI: --
发表时间: 1993
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DOI: 10.1152/ajpcell.1993.264.5.c1278
发表时间: 1993
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发表时间: 1990
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影响因子: --
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