| Project/Area Number |
15590750
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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, Instructor, 病院, 講師 (40346482)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Mari Hiroshima University, Research Institute for Radiation Biology, Research Associate, 原爆放射線医科学研究所, 助手 (30359898)
YOSHIZUMI Masao Hiroshima University, Graduate school of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (20282626)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | vascular smooth muscle cell / hypertension / atherosclerosis / signal transduction / Mnk / Mnk1 |
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| Research Abstract |
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.
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