亚砷酸钠对核转录因子Nrf2和血红素单加氧酶-1表达的影响

Effects of Sodium Arsenite on Expression of Transcription Factor Nrf2 and Heme Oxygenase 1 in Chang Liver Cells

目的观察亚砷酸钠(NaAsO2,sodium arsenite)对Chang肝细胞核转录因子Nrf2(transcription factor NF-E2-related factor 2)及血红素单加氧酶-1(hemeoxy genase1,HO-1)蛋白表达的影响,并应用谷胱甘肽(GSH)合成抑制剂丁硫氨酸亚矾胺(buthionine sulfoximine,BSO)探讨NaAsO2诱导Nrf2和HO-1蛋白活化的可能机制。方法不同浓度NaAsO2(5、10、20μmol/L)单独作用Chang肝细胞24h;同时将Chang肝细胞用BSO(3mmol/L)预处理12h后,再用NaAsO2(5、10、20μmol/L)作用24h。以Western Blot法检测细胞Nrf2和HO-1的蛋白表达。结果5、10和20μmol/LNaAsO2单独作用显著提高细胞Nrf2和HO-1蛋白含量;BSO预处理组细胞Nrf2和HO-1的蛋白表达则更显著高于NaAsO2单独作用组(P<0.01)。结论无机砷能够诱导细胞Nrf2和HO-1蛋白活化;细胞内巯基可能对无机砷诱导的Nrf2和HO-1蛋白活化具有重要作用。

Objective To observe the effects of sodium arsenite （NaAsO2） on the expression of transcription factor nrf2 （Nrf2） and heine oxygenase 1 （HO-1） in Chang liver cells, and to explore the possible mechanism by using buthionine sulfoximine （BSO）, a GSH synthesis inhibitor. Methods Chang liver cells were treated with NaAsO2 at the doses of 5, 10 and 20 μmol/L, alone, for 24 h, or pretreated with BSO （3 mmol/L, 12 h）. Western blot assays were used to detect the protein expression of Nrf2 and HO-1. Results The protein expression of Nrf2 and HO-1 significantly increased in 5, 10 and 20 μmol/L of NaAsO2 alone groups, and Nrf2 and HO-1 protein expression was up-regulated even higher by BSO pretreatment （P〈0.01）. Conclusion Inorganic arsenic can induce Nrf2 and HO-1 protein expression, and the possible mechanism involves the roles of intraeellular sulfhydryl group.