Sodium selenite-induced activation of DAPK promotes autophagy in human leukemia HL60 cells
Sodium selenite-induced activation of DAPK promotes autophagy in human leukemia HL60 cells
复制标题
亚硒酸钠诱导的 DAPK 激活促进人白血病 HL60 细胞自噬
DOI：
10.5483/bmbrep.2012.45.3.194
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发表时间：
2012-03-31
期刊：
影响因子：
3.8
通讯作者：
Xu, Caimin
中科院分区：
文献类型：
--
作者：
Jiang, Qian;Li, Feng;Xu, Caimin
尽管许多物种的证据表明自噬代表了细胞在压力下的生存策略，但自噬已被认为是非凋亡死亡的一种可能机制。从我们以前的研究结果，超营养剂量的亚硒酸钠诱导人白血病细胞凋亡，现在我们显示自噬细胞死亡后，亚硒酸钠暴露在HL 60细胞，提出了一个潜在的治疗性质的替代机制。此外，死亡相关蛋白激酶（DAPK）在此过程中表达显著增加，同时Ser（308）的磷酸化水平逐渐降低。我们进一步揭示了依赖于亚硒酸盐激活的ERK的DAPK的上调对自噬没有影响。然而，通过PP 2A介导的Ser（308）去磷酸化激活DAPK作为自噬诱导的新策略。以上结果表明，PP 2A介导的DAPK激活可使HL 60细胞对亚硒酸钠敏感，最终触发自噬细胞死亡途径，导致细胞死亡。[BMB报告2012; 45（3）：194-199]
Autophagy has been suggested as a possible mechanism for non-apoptotic death despite evidence from many species that autophagy represents a survival strategy of cells under stress. From our previous findings that supranutritional doses of sodium selenite induced apoptosis in human leukemia cells, now we show autophagic cell death occurred after selenite exposure in HL60, suggested an alternative mechanism for the potential therapeutic properties of selenite. Additionally, Death-associated Protein Kinase (DAPK) performed a significantly increased expression during this process, concomitantly with gradually decreased phosphorylation at Ser(308). We further reveal that the up-regulation of DAPK which depends on selenite-activated ERK had no effect on autophagy. However, activation of DAPK via PP2A-mediated dephosphorylation at Ser(308) serves as a new strategy for autophagy induction. In conclusion, these results indicate that PP2A-mediated activated DAPK sensitizes HL60 cells to selenite, ultimately triggers autophagic cell death pathway to commit cell demise. [BMB reports 2012; 45(3): 194-199]