| Project/Area Number |
17590737
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
ISHIDA Takafumi Hiroshima University, Hospital, Assistant Professor, 病院, 講師 (40346482)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Mari Hiroshima University, Graduate School of Biomedical Sciences, Assistant Professor, 大学院医歯薬学総合研究科, 講師 (30359898)
TASHIRO Satoshi Hiroshima University, Research Institute for Radiation Biology, Professor, 原爆放射線医科学研究所, 教授 (20243610)
FUKUNAGA Rikiro Osaka University, Graduate School of Frontier Biosciences, Associate Professor, 大学院生命機能研究科, 助教授 (40189965)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | hypertension / oxidative stress / signal transduction / Mnk / 血管平滑筋 |
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| Research Abstract |
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.
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