Nrf2通过调控EZH2的表达促进DMSO诱导的MEL细胞红系分化

Nrf2 Contributes to DMSO-induced Erythroid Differentiation in MEL Mouse Erythroleukemia Cells by Regulating EZH2 Expression

目的探讨Nrf2/EZH2通路参与DMSO诱导MEL细胞红系分化的作用及相关分子机制。方法以MEL细胞为靶细胞,DMSO为刺激源,联苯胺染色法检测细胞红系分化情况;免疫印迹检测EZH2和Nrf2蛋白表达水平。结果 DMSO可显著诱导MEL细胞红系分化,同时EZH2和Nrf2表达水平也明显升高。通过使用Nrf2诱导剂TBHQ及Nrf2 shRNA,证明Nrf2调控MEL细胞中EZH2的表达。敲低Nrf2和EZH2的表达能够抑制DMSO诱导的MEL细胞红系分化。结论Nrf2可通过调控EZH2的蛋白水平从而发挥促进MEL细胞红系分化的作用。

Objective To explore the role of Nrf2/EZH2 in mediating erythroid differentiation in mouse erythroleukemia cells under DMSO exposure. Methods MEL cells were treated with DMSO. Erythroid differentiation was detected by bezidine staining. The expression levels of Nrf2 and EZH2 were determined by western blotting. Results DMSO induced erythroid differentiation in MEL cells, along with significant induction of Nrf2 and EZH2 expression. TBHQ, a selective Nrf2 activator, increased the protein level of Nrf2. Interestingly, TBHQ also induced EZH2 expression. The lentiviral particle containing Nrf2 short hairpin RNA （shRNA） efficiently blocked TBHQ-induced EZH2 levels. Moreover, Nrf2 or EZH2 shRNA significantly inhibited DMSO-induced erythroid differentiation. Conclusion Nrf2 induction is involved in MELerythroid differentiation under DMSO exposure by regulating EZH2.