Chronic activation of glomerular mitogen-activated protein kinases in Dahl salt-sensitive rats.
Chronic activation of glomerular mitogen-activated protein kinases in Dahl salt-sensitive rats.
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Dahl 盐敏感大鼠中肾小球丝裂原激活蛋白激酶的慢性激活。
DOI：
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发表时间：
2000
影响因子：
13.6
通讯作者：
H. Iwao
中科院分区：
文献类型：
--
作者：
A. Hamaguchi;Shokei Kim;Y. Izumi;H. Iwao
有丝分裂原活化蛋白激酶（MAPK）在肾小球损伤发展中的体内作用尚不清楚。本研究检测了盐致高血压大鼠肾小球损伤中MAPK的活性，包括细胞外信号调节激酶（ERK）、c-Jun nh2末端激酶（JNK）和转录因子、激活蛋白-1 （AP-1）。6周龄的Dahl盐敏感大鼠（Dahl- s）和耐盐大鼠（Dahl- r）分别饲喂高盐（8.0% NaCl）饮食1、5和10周。在Dahl-S大鼠中，如凝胶激酶测定所示，高盐饮食引起的血压升高伴随着肾小球ERK和JNK的慢性激活，这种激活持续到高盐饮食后10周。Western blot分析显示，高盐饮食使Dahl-S大鼠肾小球ERK和JNK蛋白表达显著增加。通过凝胶迁移位移测定，ERK和JNK的激活与肾小球AP-1 DNA结合活性的增加有关。另一方面，在喂食高盐饮食的Dahl-R大鼠中，血压在整个实验过程中保持正常。然而，Dahl-R大鼠的肾小球ERK和JNK活性以及AP-1 DNA结合活性在高盐饮食治疗1或5周后没有受到影响，但在高盐饮食治疗10周后显著升高，这表明慢性钠超载本身刺激了肾小球ERK、JNK和AP-1活性。在Dahl-S和Dahl-R大鼠中，这些激酶的激活都伴随着尿蛋白排泄和肾脏生长的增加。这些观察结果为盐敏感性高血压引起肾小球ERK和JNK的慢性激活，可能导致AP-1的激活提供了第一个证据。因此，肾小球MAPK可能与盐诱导肾小球损伤的发生有关。
The in vivo role of mitogen-activated protein kinases (MAPK) in the development of glomerular injury is poorly understood. In the present study, glomerular MAPK activities, including extracellular signal-regulated kinases (ERK), c-Jun NH2-terminal kinases (JNK), and transcriptional factor, activator protein-1 (AP-1) were examined in glomerular injury of salt-induced hypertensive rats. Six-week-old Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were maintained on a high-salt (8.0% NaCl) diet for 1, 5, and 10 wk. In Dahl-S rats, as shown by in-gel kinase assay, an increase in BP by a high-salt diet was followed by chronic activation of glomerular ERK and JNK, which continued until 10 wk after a high-salt diet. Western blot analysis demonstrated a significant increase in the protein expression of glomerular ERK and JNK in Dahl-S rats fed a high-salt diet. As determined by gel-mobility shift assay, ERK and JNK activations were associated with an increase in glomerular AP-1 DNA binding activity. On the other hand, in Dahl-R rats fed a high-salt diet, BP remained normal throughout the experiments. However, glomerular ERK and JNK activities and AP-1 DNA binding activity in Dahl-R rats were not affected by 1 or 5 wk of a high-salt diet, but significantly increased by 10 wk of treatment with a high-salt diet, indicating that chronic sodium overload itself stimulated glomerular ERK and JNK and AP-1 activities. These kinase activations in both Dahl-S and Dahl-R rats were accompanied by an increase in urinary protein excretion and renal growth. These observations provide the first evidence that salt-sensitive hypertension causes chronic activation of glomerular ERK and JNK, probably leading to the activation of AP-1. Thus, glomerular MAPK may be responsible for the development of salt-induced glomerular injury.
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影响因子：
8.3
作者：
Force, T;Bonventre, JV
通讯作者：
Bonventre, JV
DOI：
10.1016/s0021-9258(18)82362-6
发表时间：
1993-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Davis
通讯作者：
R. Davis
DOI：
10.1152/ajprenal.1990.258.5.f1409
发表时间：
1990
期刊：
The American journal of physiology
影响因子：
--
作者：
Daniels,BS;Hostetter,TH
通讯作者：
Hostetter,TH
在未肾切除的 SHR 中，限盐在减少肾肥大和损伤方面优于利尿剂。
DOI：
10.1152/ajprenal.1990.258.6.f1675
发表时间：
1990
期刊：
The American journal of physiology
影响因子：
--
作者：
Benstein,JA;Feiner,HD;Parker,M;Dworkin,LD
通讯作者：
Dworkin,LD
Interleukin-1 beta 激活系膜细胞中丝裂原激活蛋白激酶的 c-jun NH2 末端激酶亚组。
DOI：
10.1152/ajprenal.1996.270.4.f634
发表时间：
1996
期刊：
The American journal of physiology.
影响因子：
--
作者：
Guan,Z;Tetsuka,T;Baier,LD;Morrison,AR
通讯作者：
Morrison,AR