PFKFB3参与了11'-deoxyverticillin A(C42)诱导的HeLa细胞自噬和凋亡

PFKFB3 regulates 11'-deoxyverticillin A (C42)-induced autophagy and apoptosis in HeLa cells

摘要:

摘要:【目的】明确糖酵解调节基因PFKFB3参与11-脱氧轮枝菌素A(11'-deoxyverticillin A，C42)诱导HeLa细胞自噬和凋亡中的作用。【方法】利用电镜、荧光显微镜、蛋白免疫杂交、转染、MTS 活性检测、siRNA干扰、定量RT-PCR等对C42处理的HeLa 细胞自噬和凋亡情况进行了检测。【结果】C42能够引起HeLa细胞不同的死亡。敲降自噬关键基因BECN1或LC3后，明显增加PARP-1的切割和促进C42引起的细胞活性丢失。尽管高浓度C42能更明显地抑制细胞增殖，但却不能增加细胞的自噬流;C42促进的自噬能被糖酵解调节基因PFKFB3的抑制剂所降低;而过量表达糖酵解调节基因PFKFB3能促进细胞自噬。【结论】糖酵解调节基因PFKFB3直接参与了C42诱导的HeLa细胞自噬，这种自噬的发生抑制了其诱导的细胞凋亡。

Abstract:

Abstract:［Objective］The aim is to reveal the role of PFKFB3 in 11'-deoxyverticillin A(C42)-induced autophagy and apoptosis.［Methods］Electron and fluorescence microscopy，immunoblotting，MTS assay，siRNA interference and real time PCR were used.［Results］C42 could induce multiple cell death in HeLa cells． Knockdown of either Beclin 1 or LC3，two important autophagic genes，increased both PARP-1 cleavage and cell viability loss． Although high dose of C42 triggered more cell viability loss，yet，it failed to augment autophagic flux． While PFKFB3 inhibitors attenuated C42-induced autophagy，the overexpression of PFKFB3 increased the induced autophagic flux.［Conclusion］PFKFB3 is involved in C42 induced-autophagy，which blunts the caspase-dependent apoptotic process.