Activation of glomerular mitogen-activated protein kinases in angiotensin II-mediated hypertension.
Activation of glomerular mitogen-activated protein kinases in angiotensin II-mediated hypertension.
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血管紧张素 II 介导的高血压中肾小球丝裂原激活蛋白激酶的激活。
DOI：
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发表时间：
1998
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;S. Kim;M. Yano;S. Yamanaka;H. Iwao
体内信号转导途径，负责高血压引起的肾小球损伤，仍有待澄清。在这项研究中，血管紧张素II（Ang II）诱导的高血压的影响，肾小球丝裂原活化蛋白激酶（MAPK），包括细胞外信号调节激酶（ERK）和c-jun氨基末端激酶（JNK），并对肾小球转录因子激活蛋白-1（AP-1）和Sp 1。凝胶内激酶法测定MAPK活性。凝胶迁移率变动法测定AP-1和Sp-1的DNA结合活性.清醒大鼠持续静脉输注Ang Ⅱ（1000 ng/kg/min）后血压迅速升高，肾小球p42和p44 ERK以及p46和p55 JNK迅速和短暂激活，峰值出现在15 ~ 180 min。超位移分析表明，活化的AP-1复合物中含有c-Fos和c-Jun蛋白。另一方面，肾小球Sp 1 DNA结合活性在血管紧张素II输注7天内没有改变。这些结果提供了第一个体内证据表明，血管紧张素II诱导的高血压引起肾小球ERK和JNK的激活，导致AP-1的激活。因此，ERK和JNK信号通路，通过激活AP-1，可能涉及高血压诱导的肾小球损伤的发展。
The in vivo signal transduction pathway, responsible for hypertension-induced glomerular injury, remains to be clarified. In this study, the effect of angiotensin II (Ang II)-induced hypertension was examined on glomerular mitogen activated protein kinases (MAPK), including extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK), and on glomerular transcription factors activator protein-1 (AP-1) and Sp 1. MAPK activities were determined by in-gel kinase assay. DNA binding activity of AP-1 and Sp 1 was determined by gel mobility shift assay. Continuous infusion of Ang II (1000 ng/kg per min, intravenously) to conscious rats rapidly increased BP, followed by the rapid and transient activation of glomerular p42 and p44 ERK and p46 and p55 JNK with the peak at 15 to 180 min. Glomerular AP-1 binding activity was increased 2.6-fold (P < 0.01) at 24 h after the start of Ang II infusion. Supershift analysis showed that the activated AP-1 complexes contained c-Fos and c-Jun proteins. On the other hand, glomerular Sp 1 DNA binding activity was not changed throughout 7 d of Ang II infusion. These results provided the first in vivo evidence that Ang II-induced hypertension causes the activation of glomerular ERK and JNK, leading to the activation of AP-1. Thus, ERK and JNK signaling cascades, via the activation of AP-1, may be implicated in the development of hypertension-induced glomerular injury.
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影响因子：
15.9
作者：
KAGAMI, S;BORDER, WA;NOBLE, NA
通讯作者：
NOBLE, NA
DOI：
10.1073/pnas.89.20.9759
发表时间：
1992-10-15
影响因子：
11.1
作者：
KRIWACKI, RW;SCHULTZ, SC;CARADONNA, JP
通讯作者：
CARADONNA, JP
影响因子：
15.9
作者：
Xu, QB;Liu, YS;Holbrook, NJ
通讯作者：
Holbrook, NJ
影响因子：
13.2
作者：
BORDER, WA;NOBLE, NA
通讯作者：
NOBLE, NA