Differential Myocyte Response to Strain Vectors and Rate

肌细胞对应变向量和速率的差异反应

• 批准号: 7114911
• 负责人: SAMUEL SENYO
• 金额: $ 3.94万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-16 至 2008-11-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7114911
• 关键词: SDS polyacrylamide gel electrophoresis; biomechanics; cardiac myocytes; focal adhesion kinase; heart contraction; immunocytochemistry; laboratory rat; mechanical stress; phosphorylation; predoctoral investigator; protein kinase; protein kinase C; protein localization; protein transport; tissue /cell culture; western blottings

DESCRIPTION (provided by applicant): Biomechanical forces play a dynamic role in cardiac muscle adaptation and disease. Mechanical deformation includes tensile, compressive, and shear stress. There is growing evidence that cells discriminate different vectors of mechanical stress and rate of application. However, the mechanism by which cells detect complex cyclic mechanical stimulus is poorly understood. Phosphorylation and translocation of proteins associated with the costamere or z-disc may mediate mechanotransduction of vector forces and rates of stress and include focal adhesion kinase (FAK), Rho kinase A (Rho), and protein kinase C (PKC). Insufficient data exists on the behavior of these proteins in cardiac muscle to mechanical strain vectors and even less in the response to strain application rates. Therefore, the hypothesis is that the direction and rate of mechanical strain regulates protein phosphorylation and localization in cardiac myocytes. Orienting cells will direct the delivery of strain vectors by plating rat neonatal cardiac myocytes on novel three-dimensional substrata. Western blotting and immunocytochemistry will evaluate phosphorylation and localization of FAK, Rho, and PKCepsilon to cyclic mechanical activity.

描述(由申请人提供)：生物力学力量在心肌适应和疾病中起着动态作用。机械变形包括拉应力、压应力和剪应力。越来越多的证据表明，细胞可以区分不同的机械应力矢量和应用率。然而，细胞检测复杂的周期性机械刺激的机制还知之甚少。与胞间或Z-盘相关的蛋白质的磷酸化和易位可能介导向量力和应激速率的机械转导，包括粘着斑激酶(FAK)、Rho激酶A(Rho)和蛋白激酶C(PKC)。关于心肌中这些蛋白质对机械应变载体的行为的数据不足，对应变应变率的响应数据更少。因此，假设机械应变的方向和速率调节心肌细胞中蛋白质的磷酸化和定位。定向细胞将通过在新的三维基质上电镀新生大鼠心肌细胞来指导应变载体的输送。Western blotting和免疫细胞化学将评估FAK、Rho和PKCepsilon的磷酸化和定位对循环机械活性的影响。