The role of MNK1/2 in cardiovascular remodeling

MNK1/2在心血管重塑中的作用

• 批准号: 17590737
• 负责人: ISHIDA Takafumi
• 金额: $ 2.05万
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590737/
• 关键词: hypertension; oxidative stress; signal transduction; Mnk; 血管平滑筋

We have demonstrated that Mnk1/2 are involved in angiotensin II (AngII)-mediated protein synthesis and hypertrophy, presumably through the activation of translation-initiation in vascular smooth muscle cells (VSMC).In the present study, we showed oxidative stress also potently activated Mnk1/2. Oxidative stress-induced Mnk activation was dependent on Ras, ERK and p38MAP kinase. Mnk1 activated by oxidative stress translocated into the nucleus and co-localized with PML body.The protein expression of Ets-1, a transcription factor, stimulated by PDGF or FGF was abolished in VSMC from Mnk1-/-Mnk2-/-mice, which was independent of mRNA level. Similarly, siRNA against Mnk1/2 significantly decreased AngII-induced Ets-1 protein expression, and osteopontin expression, one of the target genes of Ets-1.These data suggest that Mnk1/2 regulate the expression of a certain proteins at the translational level, and may be potential targets for atherosclerotic vascular diseases. In addition, these data indicate that Mnk1/2 have undefined functions in translational machinery and nucleus.

我们已经证明，Mnk 1/2参与血管紧张素II（AngII）介导的蛋白质合成和肥大，可能是通过激活血管平滑肌细胞（VSMC）的收缩起始。氧化应激诱导的Mnk激活依赖于Ras、ERK和p38 MAP激酶。Mnk 1-/-Mnk 2-/-小鼠VSMC经PDGF或FGF刺激后，Ets-1蛋白表达被抑制，但与mRNA水平无关。同样，针对Mnk 1/2的siRNA可显著降低AngII诱导的Ets-1蛋白表达，并降低Ets-1靶基因之一骨桥蛋白的表达。这些数据表明，Mnk 1/2在翻译水平上调节某些蛋白的表达，可能是动脉粥样硬化性血管疾病的潜在靶点。此外，这些数据表明，Mnk 1/2在翻译机器和核中的功能尚未确定。

项目成果

Beneficial effect of T-type calcium channel blockers on endothelial function in patients with essential, hypertension.

T 型钙通道阻滞剂对原发性高血压患者内皮功能的有益作用。

• 发表时间: 2005
• 期刊: Hypertension Research 28
• 作者: Oshima;Tetsuya
• 通讯作者: Tetsuya

Role of the JNK pathway in thrombin-induced ICAM-1 expression in endothelial cells

• DOI: 10.1016/j.cardiores.2005.05.029
• 发表时间: 2005-11-01
• 期刊: CARDIOVASCULAR RESEARCH
• 影响因子: 10.8
• 作者: Miho, N;Ishida, T;Chayama, K
• 通讯作者: Chayama, K

Beneficial effect of T-type calcium channel blockers on endothelial function in patients with essential hy pertension.

T型钙通道阻滞剂对原发性高血压患者内皮功能的有益作用。

• 发表时间: 2005
• 期刊: Hypertension Research 28
• 作者: Oshima T;Ishida T et al.
• 通讯作者: Ishida T et al.

Genetic ablation of the transcription repressor Bachl leads to myocardial protection against ischemia/reperfusion in mice.

转录抑制因子 Bachl 的基因消除可保护小鼠心肌免受缺血/再灌注。

• 发表时间: 2006
• 期刊: Genes to Cells 11
• 作者: Yano;Yoko
• 通讯作者: Yoko

Genetic ablation of the transcription repressor Bach1 leads to myocardial protection against ischemia/reperfusion in mice

• DOI: 10.1111/j.1365-2443.2006.00979.x
• 发表时间: 2006-07-01
• 期刊: GENES TO CELLS
• 影响因子: 2.1
• 作者: Yano, Yoko;Ozono, Ryoji;Igarashi, Kazuhiko
• 通讯作者: Igarashi, Kazuhiko