HIF-2α通过内质网应激途径诱导LO2细胞凋亡

HIF-2αinduces apoptosis of LO2 cells via endoplasmic reticulum stress signaling pathway

目的探讨缺氧诱导因子2α(HIF-2α)在缺氧诱导LO2肝细胞凋亡中的作用及其机制。方法构建HIF-2α特异性的沉默干扰RNA(siRNA)并转染LO2细胞,分别在常氧及缺氧条件下培养细胞,采用流式细胞术检测细胞凋亡,Western blot法检测内质网应激及细胞凋亡相关蛋白的表达。结果与常氧条件相比,缺氧处理后HIF-2α表达、细胞凋亡、内质网应激与凋亡相关蛋白表达均明显增加,而siRNA能有效抑制上述指标的增加过程。结论缺氧条件下HIF-2α通过内质网应激途径引发LO2细胞凋亡,可能是缺氧性肝脏疾病治疗的一个潜在靶点。

Objective To investigate the effect and underlying mechanism of hypoxia-inducible factor-2α（HIF-2α） on apoptosis of LO2 cells induced by hypoxia. Methods HIF-2α-targeted siRNA was constructed and transfected into LO2 cells, which were cultured under normoxia and hypoxia conditions in different times. Cell apoptosis was detected by flow cytometry, and the expressions of key proteins relevant to endoplasmic reticulum （ER） stress and apoptosis were determined by Western blot. Results Compared with normoxia group, HIF-2α expression, cell apoptosis and expressions of key proteins relevant to ER stress and apoptosis were all significantly increased in hypoxia-treated LO2 cells,which was effectively inhibited by siRNA. Conclusion HIF-2α can induce cell apoptosis by activating ER stress signaling pathway under hypoxia condition, which may be a potential target in the treatment of hypoxia-relevant liver diseases.