(R)-(+)-Blebbistatin

(R)-(+)-Blebbistatin是一种细胞可透过性的非肌肉肌球蛋白II型ATP酶抑制剂,IC50值为2 μM [1,2].

非肌肉肌球蛋白II(NM II)是一种肌动蛋白结合蛋白,在调节细胞迁移\黏附及分化中发挥主要作用[4].用基因缺失和突变的方法更加证实了NM II在这些过程中的重要性,NM II突变影响了大范围的蛋白功能,且引发单基因病[5.6].

(R)-(+)-Blebbistatin是一种小分子抑制剂,与肌球蛋白-ADP-Pi复合体优先结合以放慢磷酸盐的释放[2].该抑制剂完全消除肌动蛋白激活的Mg-ATP酶的收缩活性和体外几种物种的肌球蛋白II的运动性(IC50 = 0.5-5.0 μM) [8,9],但是,它对平滑肌肌球蛋白II (IC50 =80 μM)\肌球蛋白I\V及X的效果差[3].此外,blebbistatin能够强效抑制哺乳动物动脉平滑肌(IC50=5 μM) [9].在体内应用中,blebbistatin所具有的阻滞处于肌动蛋白分离状态的肌球蛋白II及阻止刚性肌动球蛋白交联的特性是一个巨大优势[2,11].

在恒压灌注模型系统中,CB和TM细胞用blebbistatin (10-200 M)处理后,细胞形态有所变化,肌动蛋白应力纤维含量减少.经过24小时的冲刷,Blebbistatin效果是完全可逆的[10].Blebbistatin抑制单细胞收缩而不改变细胞内钙瞬变的形态(IC50 = 0.43 μM).暴露于波长小于488 nm的紫外光下也可迅速抑制blebbistatin[8].

参考文献：
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