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The function of Mnk1 in vascular smooth muscle cells

Mnk1在血管平滑肌细胞中的功能

基本信息

批准号：
15590750
负责人：
ISHIDA Takafumi
金额：
$ 2.18万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590750/
关键词：
vascular smooth muscle cell hypertension atherosclerosis signal transduction Mnk Mnk1

项目摘要

Angiotensin II(AngII) treatment resulted in increased Mnk1 activity and eIF4E phosphorylation in rat vascular smooth muscle cells(VSMC). Expression of a dominant-negative Mnk1 mutant abolished AngII-induced eIF4E phosphorylation. ERK, but not p38MAP kinase, was required for angII-induced Mnk1-eIF4E activation. Further, dominant-negative constructs for Ras, but not for Rho or Rac, abolished angII-induced Mnk1 activation. Treatment of VSMC with a specific inhibitor of Mnk1 resulted in dose-dependent decreases in angII-stimulated protein synthesis and VSMC hypertrophy. These data demonstrated that : (1)angII-induced Mnk1 activation is mediated by the Ras-ERK cascade in VSMC, and (2)Mnk1 is involved in angII-mediated protein synthesis and hypertrophy, presumably through the activation of translation-initiation.Hydrogen peroxide potently activated Mnk1 via ERK, p38MAP kinase and c-Src-dependent mechanisms. Mnk1 activated by oxidative stress translocated into the nucleus, indicating undefined functions of Mnk1.2D-gel electrophoresis revealed that several spots for phospho-proteins were increased in VSMC transfected with active Mnk1, suggesting the existence of novel Mnk1 substrates in the nucleus.In summary, Mnk1 may provide new insights into molecular mechanisms involved in cardiovascular remodeling.

血管紧张素II（AngII）处理导致大鼠血管平滑肌细胞（VSMC）中Mnk 1活性和eIF 4 E磷酸化增加。显性负性Mnk 1突变体的表达消除了AngII诱导的eIF 4 E磷酸化。ERK而不是p38 MAP激酶是angII诱导的Mnk 1-eIF 4 E激活所必需的。此外，显性负结构的Ras，但不是Rho或Rac，废除血管紧张素II诱导的Mnk 1激活。用Mnk 1特异性抑制剂治疗VSMC导致AngII刺激的蛋白质合成和VSMC肥大呈剂量依赖性降低。这些数据表明：（2）Mnk 1参与了血管紧张素Ⅱ介导的蛋白质合成和肥大，推测其可能通过激活血管紧张素Ⅱ的促凋亡起始途径，过氧化氢通过ERK、p38 MAP激酶和c-Src依赖性机制激活Mnk 1。Mnk 1在氧化应激条件下被激活，并移位到细胞核内，提示Mnk 1的功能尚未明确。双向电泳结果显示，转染Mnk 1的VSMC磷酸化蛋白质点增多，提示细胞核内存在新的Mnk 1底物。

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Effect of amlodipine and cilazapril treatment on platelet Ca2+ handling in spontaneously hypertensive rats.

DOI：
10.1291/hypres.26.901
发表时间：
2003-11
期刊：
Hypertension research : official journal of the Japanese Society of Hypertension
影响因子：
0
作者：
T. Oshima;N. Ono;R. Ozono;Y. Higashi;M. Ishida;T. Ishida;N. Miho;H. Nakashima;Y. Yano;M. Kambe
通讯作者：
T. Oshima;N. Ono;R. Ozono;Y. Higashi;M. Ishida;T. Ishida;N. Miho;H. Nakashima;Y. Yano;M. Kambe

Mnk1 is required for angiotensin II - Induced protein synthesis in vascular smooth muscle cells