Intracellular Signaling of Stretch Mediated Myocyte Growth

拉伸介导的肌细胞生长的细胞内信号转导

• 批准号: 03454247
• 负责人: YAZAKI Yoshio
• 金额: $ 4.16万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454247/
• 关键词: 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

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.

为了研究机械刺激诱导原癌基因表达的分子机制，我们在可变形培养皿中培养大鼠新生心肌细胞，并通过拉伸贴壁细胞施加体外机械负荷。肌细胞拉伸增加总细胞RNA含量和mRNA水平的c-fos和骨骼α-肌动蛋白随后激活蛋白质合成。CAT分析表明，含有血清反应元件的序列是c-fos基因通过拉伸有效转录所必需的。蛋白激酶C抑制剂可在转录水平上抑制c-fos mRNA的积累，并通过下调蛋白激酶C而显著抑制c-fos mRNA的积累。此外，肌细胞拉伸增加磷酸肌醇水平。这些结果表明，机械刺激可能直接诱导原癌基因的表达，可能通过蛋白激酶C激活。此外，我们还观察了牵张对有丝分裂原激活蛋白激酶（MAP）的激活作用。这一结果表明，MAP激酶的激活可能会增加由机械刺激诱导的核糖体蛋白质合成的效率。

项目成果

Y.Yazaki,I.Komuro: "New Aspects in the Treatment of Failing Heart" Springer-Verlag Tokyo, 237 (1992)

Y.Yazaki、I.Komuro：“治疗衰竭心脏的新方面” Springer-Verlag Tokyo，237（1992）

I.Shiojima,I.Komuro,K.Ieki,R.Nagai,Y.Yazaki: "Molecular mechanism of diastolic dysfunction in pressure overload cardiac hypertrophy." Jpn.Circ.J.56(Suppl.5). 1268-1272 (1992)

I.Shiojima，I.Komuro，K.Ieki，R.Nagai，Y.Yazaki：“压力超负荷心脏肥大舒张功能障碍的分子机制。”

I.Shiojima, I.Komuro, K.Ieki, R.Nagai, Y.Yazaki: "Molecular mechanism of diastolic dysfunction in pressure overload cardiac hypertrophy." Jpn. Circ. J.56(Suppl.5). 1268-1272 (1992)

I.Shiojima、I.Komuro、K.Ieki、R.Nagai、Y.Yazaki：“压力超负荷心脏肥大舒张功能障碍的分子机制”。

Y.Seko,T.Yamazaki,Y.Shinkai,H.Yagita,K.Okumura,S.Naito,K.Imataka,J.Fujii,Y.Yazaki:"Cellular and molecular bases for the immunopathology of the myocardial cell damage in-volved in acute viral myocarditis with special reference to dilated cardiomyopathy." J

Y.Seko，T.Yamazaki，Y.Shinkai，H.Yagita，K.Okumura，S.Naito，K.Imataka，J.Fujii，Y.Yazaki：“心肌细胞损伤免疫病理学的细胞和分子基础

K.Maemura,H.Kurihara,T.Morita,Y.Ohhashi,Y.Yazaki: "Pro-duction of endothelin-1 in vascular endothelial cells is regulated by factors associated with vascular injury." Gerontology. 38(Suppl.1). 29-35 (1992)

K.Maemura、H.Kurihara、T.Morita、Y.Ohhashi、Y.Yazaki：“血管内皮细胞中内皮素-1 的产生受到与血管损伤相关的因素的调节。”