Mechanical control of energy metabolism in cardiomyocytes

心肌细胞能量代谢的机械控制

• 批准号: 24657127
• 负责人: OGURA Toshihiko
• 金额: $ 2.66万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24657127/
• 关键词: 細胞力覚; エネルギー代謝; 心筋; 力刺激; エネルギー; 酸化的リン酸化

Beating heart maintains constant circulation by responding to hemodynamics changes, such as altering blood pressure and heart rate. To adapt to high blood pressure, for example, cardiomyocytes must produce more ATP to contract even under the high mechanical overload. To explore a functional link between mechanical stimuli and energetic compensation, we searched for factors that respond to mechanical forces, and found a transcriptional co-activator that shuttles from cytoplasm to nucleus in response to physical force. This co-activator robustly activates nuclear receptors that regulate lipid metabolism in beating cardiomyocytes. As a result, this co-activator increases ATP production by enhancing oxidative phosphorylation (OxPhos) in mitochondria. Our finding provides an essential and novel insight on the energetic adaptation mechanism, in which drug targets can be found for therapy of heart diseases, such as heart failure.

跳动的心脏通过响应血流动力学的变化来维持恒定的循环，例如改变血压和心率。例如，为了适应高血压，心肌细胞必须产生更多的ATP，即使在高机械负荷下也能收缩。为了探索机械刺激和能量补偿之间的功能联系，我们寻找了对机械力做出反应的因素，并发现了一种转录辅激活因子，它响应于物理力从细胞质穿梭到细胞核。这种辅激活剂强烈激活调节跳动心肌细胞中脂质代谢的核受体。因此，这种共激活剂通过增强线粒体中的氧化磷酸化（OxPhos）来增加ATP的产生。我们的发现为能量适应机制提供了一个重要的和新的见解，其中可以找到治疗心脏疾病（如心力衰竭）的药物靶点。

项目成果

生命現象を力を視点に再解釈する

从权力的角度重新诠释生命现象

• 发表时间: 2012
• 作者: Y. Hirota;M. Sawada;Y. S. Kida;S. Huang;O. Yamada;M. Sakaguchi;T. Ogura;H. Okano;K. Sawamoto.;小椋利彦;小椋利彦;小椋利彦;小椋利彦;小椋利彦;小椋利彦
• 通讯作者: 小椋利彦

Roles of Planar Cell Polarity Signaling in Maturation of Neuronal Precursor Cells in the Postnatal Mouse Olfactory Bulb

• DOI: 10.1002/stem.1137
• 发表时间: 2012-08-01
• 期刊: STEM CELLS
• 影响因子: 5.2
• 作者: Hirota, Yuki;Sawada, Masato;Sawamoto, Kazunobu
• 通讯作者: Sawamoto, Kazunobu

Fibroblast growth factor 10 gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic switch for down-regulation in the myocardium

• DOI: 10.1073/pnas.1215360109
• 发表时间: 2012-10
• 期刊: Proceedings of the National Academy of Sciences
• 作者: Yusuke Watanabe;S. Zaffran;A. Kuroiwa;Hiroaki Higuchi;T. Ogura;R. Harvey;R. Kelly;M. Buckingham

生命現象を力を視点に再解釈するために

从权力的角度重新诠释生命现象

• 发表时间: 2013
• 作者: Y. Hirota;M. Sawada;Y. S. Kida;S. Huang;O. Yamada;M. Sakaguchi;T. Ogura;H. Okano;K. Sawamoto.;小椋利彦;小椋利彦
• 通讯作者: 小椋利彦

生命現象を力学的に再解釈する、そして、生命現象を再構築する

机械地重新诠释生命现象、重构生命现象

• 发表时间: 2014
• 作者: Y. Hirota;M. Sawada;Y. S. Kida;S. Huang;O. Yamada;M. Sakaguchi;T. Ogura;H. Okano;K. Sawamoto.;小椋利彦
• 通讯作者: 小椋利彦