| Project/Area Number |
03454247
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YAZAKI Yoshio Internal Medicine, Medicine, Professor, 医学部(病), 教授 (20101090)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAZAKI Tsutomu Internal Medicine, Medicine,, 医学部(病), 医員 (60251245)
KOMURO Issei Internal Medicine, Medicine,, 医学部(病), 医員 (30260483)
NAGAI Ryozo Internal Medicine, Medicine, Associate Professor, 医学部(病), 助教授 (60207975)
方 榮哲 東京大学, 医学部(病), 医員
世古 義規 東京大学, 医学部(病), 助手 (30240708)
栗原 裕基 東京大学, 医学部(病), 助手 (20221947)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1992: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1991: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | myocytes / mechanical stress / intracellular signaling / PI turnover / hypertrophy / proto-oncogene / 心肥大 / MAPキナーゼ / ゲル内リン酸化 / 細胞内情報伝達 / プロテインキナーゼC / 伸展刺激 / ラット / MAPキナ-ゼ / プロテインキナ-ゼC |
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| Research Abstract |
To examine the molecular mechanisms by which mechanical stimuli induce protooncogene expression, we cultured rat neonatal cardiocytes in deformable dishes and imposed an in vitro mechanical load by stretching the adherent cells. Myocyte stretching increased total cell RNA content and mRNA levels of c-fos and skeletal alpha-actin followed by activation of protein synthesis. CAT assay indicated that sequences containing a serum response element were required for efficient transcription of c-fos gene by stretching. This accumulation of c-fos mRNA was suppressed by protein kinase C inhibitors at the transcriptional level and inhibited markedly by down-regulation of protein kinase C. Moreover, myocyte stretching increased inositol phosphate levels. These findings suggest that mechanical stimuli might directly induce protooncogene expression possibly via protein kinase C activation. Furthermore, we observed the activation of mitogen activated protein (MAP) kinase by myocytes stretching. This result suggest that MAP kinase activation might increase in efficiency of protein synthesis in ribosomes induced by mechanical stimuli.
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