MEK1-ERK1/2信号调节心肌细胞非沙尔科梅里克动因细胞骨架网络
Kelly M Grimes1, Marjorie Maillet1, Casey O Swoboda1
1Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, United States.
MEK1-ERK1/2通路通过改变actin细胞骨架来影响心肌细胞的生长. 这种信号影响非sarcomeric的actin,影响心脏细胞的形状和大小在过度缩小.
科学领域:
- 心血管生物学 心血管生物学
- 细胞信号传递 细胞信号传递
- 分子心脏病学分子心脏病学
背景情况:
- 心脏缩包括心室重塑,导致扩张或集中几何形状.
- MEK1-ERK1/2通路与心肌细胞的差异生长有关 (加厚与延长).
- 控制MEK1-ERK1/2对心肌细胞定向生长的影响机制尚不清楚.
研究的目的:
- 研究心肌细胞中MEK1-ERK1/2信号传递的下游效应因子.
- 为了确定这种途径是如何调节心肌细胞生长和几何的.
- 探索细胞骨蛋白在MEK1-ERK1/2-介导的心脏重塑中的作用.
主要方法:
- 用激活的MEK1或U0126抑制剂治疗的培养新生儿大鼠心室肌细胞的不偏的光蛋白质查.
- 生物信息分析以识别差异酸化蛋白质.
- 在转基因和基因被删除的小鼠中进行西式涂抹和体内研究,以验证研究结果.
主要成果:
- 蛋白质组分析揭示了细胞骨蛋白质是差异化蛋白质的最大子集.
- MEK1-ERK1/2信号操纵改变了细胞骨蛋白质酸化.
- 激活的MEK1和ERK1/2-缺陷的心脏显示了心肌细胞中非sarcomericactin表达的增加.
- 细胞质 β-和 γ-actin 异型在皮层下细胞内区域增加.
结论:
- MEK1-ERK1/2信号调节心肌细胞中的非sarcomeric行为细胞骨架.
- 这种调节对于控制心肌细胞宽度和长度的增长至关重要.
- 研究结果表明,MEK1-ERK1/2在指向心脏生长中的机制.
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