Restoration of YAP activation rescues HL-1 cardiomyocytes from apoptotic death by ethanol
Restoration of YAP activation rescues HL-1 cardiomyocytes from apoptotic death by ethanol
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DOI：
10.2131/jts.42.545
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发表时间：
2017-10-01
影响因子：
2
通讯作者：
Uemura, Koichi
中科院分区：
文献类型：
--
作者：
Noritake, Kanako;Aki, Toshihiko;Uemura, Koichi
我们以前报道过，当小鼠心房衍生的HL-1心肌细胞暴露于2%乙醇后发生凋亡时，细胞骨架被严重破坏，抗凋亡转录辅激活因子Yes相关蛋白（雅普）被灭活。与我们之前的观察结果一致，结缔组织生长因子（CTGF），一种抗凋亡生长因子和雅普的靶点，在暴露于2%乙醇期间以时间依赖性方式降低。雅普激活的恢复拯救了细胞免于凋亡：逆转录病毒介导的组成型活性雅普的表达和jasplakin对肌动球蛋白细胞骨架的稳定都防止了细胞死亡。相反，雅普抑制剂对细胞死亡没有影响，证实了雅普在乙醇暴露的细胞中的失活。因此，肌动蛋白张力的降低和雅普失活应该是乙醇对HL-1心肌细胞的细胞毒性的关键。
We reported previously that when mouse atrium-derived HL-1 cardiomyocytes undergo apoptosis upon exposure to 2% ethanol, the cellular cytoskeleton is severely disrupted and the anti-apoptotic transcriptional co-activator Yes-associated protein (YAP) is inactivated. Consistent with our previous observations, the expression of connective tissue growth factor (CTGF), an anti-apoptotic growth factor and a target of YAP, decreases in a time-dependent manner during exposure to 2% ethanol. The restoration of YAP activation rescues the cells from apoptosis: both the retrovirus-mediated expression of constitutively active YAP and the stabilization of the actomyosin cytoskeleton by jasplakinolide prevent cell death. In contrast, YAP inhibitors have no effect on cell death, confirming the inactivation of YAP in ethanol-exposed cells. Thus, a decrease in actin tension and YAP inactivation should be crucially involved in the cytotoxicity of ethanol on HL-1 cardiomyocytes.