Na(+)-H+ antiporter phenotype, abundance, and phosphorylation of immortalized lymphoblasts from humans with hypertension.
Na(+)-H+ antiporter phenotype, abundance, and phosphorylation of immortalized lymphoblasts from humans with hypertension.
复制标题
高血压患者永生化淋巴母细胞的 Na( )-H 逆向转运蛋白表型、丰度和磷酸化。
DOI：
10.1161/01.hyp.25.5.971
复制
发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Krolewski,AS
中科院分区：
文献类型：
--
作者：
Ng,LL;Sweeney,FP;Siczkowski,M;Davies,JE;Quinn,PA;Krolewski,B;Krolewski,AS
先前的研究表明，高血压患者不同细胞类型的Na+-H+交换活性升高。高血压患者的EB病毒永生化的淋巴母细胞中保留了最大转运能力增加的表型。这种异常现象背后的机制尚不清楚。在这项研究中，我们使用来自高血压患者和正常血压对照组的淋巴母细胞，有或没有高血压家族史，以(1)用pH指示剂2′，7′-bis(carboxyethyl)-5(6)-carboxyfluorescein，用荧光法测定Na+-H+交换器活性；(2)用特异性多克隆抗体测定Na+-H+交换器亚型1的丰度；(3)通过免疫沉淀32P标记的转运体来测定Na+-H+交换器的磷酸化。在pH为6.0时，高血压患者和有高血压家族史的受试者细胞的Na+-H+交换活性(单位为毫米/升/分钟)显著高于正常血压受试者(12.9±0.6)。在所有三组受试者中，交换器的丰度是相同的，这表明高血压组的活动增加是由于交换器的成交量增加。高血压组静止期细胞Na+-H+交换器磷酸化水平(1.58±0.16)显著高于对照组(1.00±0.07)，有高血压家族史的正常血压组(1.23±0.14)高于正常对照组(1.23±0.14)。自发性高血压大鼠血管平滑肌细胞的Na~+-H~+交换功能和磷酸化也发生了相同的变化。我们的发现表明，高血压患者细胞中Na+-H+交换器活性的升高与交换器丰度的增加无关，但可能与交换器磷酸化的增加有关。
Previous studies have demonstrated an elevated Na+-H+exchanger activity in various cell types from patients with essential hypertension. The phenotype of an increased maximal transport capacity is preserved in Epstein-Barr virus immortalized lymphoblasts from hypertensive patients. The mechanisms underlying this abnormality are unclear. In this study, we used lymphoblasts from hypertensive patients and normotensive control subjects with and without a family history of hypertension to determine (1) Na+-H+exchanger activity using fluorometry with the pH indicator 2′,7′-bis(carboxyethyl)-5(6)-carboxyfluorescein, (2) Na+-H+exchanger isoform 1 abundance with specific polyclonal antibodies, and (3) Na+-H+exchanger phosphorylation by immunoprecipitation of the32P-labeled transporter. Na+-H+exchanger activity (in millimoles per liter per minute) measured when pHiwas clamped at 6.0 was significantly higher in cells from hypertensive patients (18.8±0.6,P<.001) and those subjects with a family history of hypertension (16.4±0.6,P<.001) compared with normotensive control subjects (12.9±0.6). Exchanger abundance was identical in all three groups of subjects, indicating that increased activity in the hypertensive group was due to an elevated turnover number of the exchanger. Na+-H+exchanger phosphorylation in quiescent cells was significantly elevated in cells from hypertensive patients (1.58±0.16,P<.001) compared with control subjects (1.00±0.07), and cells from normotensive subjects with a hypertensive family history showed intermediate values (1.23±0.14). Identical changes in Na+-H+exchanger function and phosphorylation have been demonstrated in vascular smooth muscle cells from spontaneously hypertensive rats. Our findings suggest that the elevated Na+-H+exchanger activity in cells from human hypertensive patients is not associated with an increased exchanger abundance but may be related to increased exchanger phosphorylation.
登录
查看更多内容
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。
影响因子：
15.9
作者：
D. Rosskopf;E. Frömter;W. Siffert
通讯作者：
W. Siffert
1 型糖尿病肾病患者的永生化淋巴母细胞异常 Na /H 逆向转运表型和周转。
DOI：
10.1172/jci117291
发表时间：
1994
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Ng,LL;Davies,JE;Siczkowski,M;Sweeney,FP;Quinn,PA;Krolewski,B;Krolewski,AS
通讯作者：
Krolewski,AS
冈田酸是一种磷酸酶抑制剂，可诱导 Na /H 逆向转运的激活和磷酸化。
DOI：
10.1016/s0021-9258(18)98630-8
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
L. Bianchini;M. Woodside;C. Sardet;J. Pouysségur;A. Takai;S. Grinstein
通讯作者：
S. Grinstein
通过磷核磁共振波谱检测原发性高血压患者骨骼肌运动中 Na /H 逆向转运活性异常的证据。
影响因子：
6
作者：
C. Dudley;D. Taylor;L. Ng;G. Kemp;P. Ratcliffe;G. Radda;J. Ledingham
通讯作者：
J. Ledingham
DOI：
10.1016/s0021-9258(17)36887-4
发表时间：
1994-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
B. Bertrand;Shigeo Wakabayashi;T. Ikeda;Jacques Pouysségur;M. Shigekawa
通讯作者：
B. Bertrand;Shigeo Wakabayashi;T. Ikeda;Jacques Pouysségur;M. Shigekawa