无机砷对肝细胞转录因子Nrf2及其调控蛋白表达影响  

Effects of sodium arsenite on expressions of nuclear transcription factor Nrf2 and Nrf2-regulated proteins

作　　者：刘丹[1] 李冰[1] 董丹丹[1] 邢晓越[1] 王欣[1] 李昕[1] 孙贵范[1] 

机构地区：[1]中国医科大学公共卫生学院劳动卫生教研室砷生物学作用评价及砷中毒防治辽宁省重点实验室,辽宁沈阳110001

出　　处：《中国公共卫生》2012年第9期1188-1190,共3页Chinese Journal of Public Health

基　　金：国家自然科学基金(81172611;81072243)

摘　　要：目的探讨不同时间和不同浓度亚砷酸钠(NaAsO2)暴露对Chang肝细胞株NF-E2相关因子2(Nrf2)、及其调控的下游抗氧化酶NAD(P)H:醌氧化还原酶1(NQO1)和血红素单加氧酶-1(HO-1)蛋白表达的影响。方法25μmol/L NaAsO2作用Chang肝细胞2、4、6、12和24 h;或不同浓度的NaAsO2(10、25和50μmol/L)作用Chang肝细胞6 h,免疫印迹法(western blot)检测细胞内Nrf2、NQO1和HO-1的蛋白表达情况。结果 25μmol/L的NaAsO2可以明显诱导Chang肝细胞Nrf2、NQO1和HO-1的蛋白表达(P<0.01);Nrf2蛋白2 h开始明显诱导,4 h表达水平最高,此后随暴露时间的延长虽然表达有所下降,但持续至24 h仍明显高于对照组;NQO1的蛋白表达水平也从4 h开始增加并持续至24 h;HO-1的蛋白表达则从6 h开始明显诱导,且随暴露时间的继续延长表达持续上升,具有明显的时间-效应关系;10、25和50μmol/L NaAsO2染毒6 h,Nrf2、NQO1和HO-1的蛋白表达均随染毒剂量的增加而大量诱导,具有明显的剂量-效应关系(P<0.01)。结论 NaAsO2暴露能够诱导Chang肝细胞Nrf2、NQO1和HO-1蛋白表达增强,且具有一定的剂量-效应关系。Objective To explore the effects of sodium arsenite （ NaAsO2 ） on the protein expression of transcription factor nuclear factor erythroid 2-related factor 2 （Nrf2） and Nrf2-regulated downstream anti-oxidant enzymes in Chang liver cells. Methods Chang liver cells were treated with NaAsO2 （25 mol/L） for 2,4,6,12, and 24 hours or NaAsO2 at different doses of 10,25, and 50 mol/L for 6 hours. Western blot assay was used to detect the protein expression of Nrf2, NAD （P） H ： quinone oxidoreductase （ NQO1 ）, and heme oxygenase-1 （ HO-1 ）. Results NaAsO2 exposure of 25 p.mol/L could significantly induce Nrf2 ,NQO1, and HO-1 protein expressions in Chang liver cells. Nrf2 protein level was higher than control cells 2 hours after NaAsO2 exposure and approached the peak 4 hours after the exposure. NQOI protein level increased from 4 to 24 hours after the exposure. The protein expression of HO-1 was induced 6 hours after the exposure with a time-effect response. When the cells were treated with 10,25, and 50 μmol/L of NaAsO2 for 6 hours, dose-effect response was observed. Conclusion NaAsO2 could increase protein expression of Nrf2, NQO1, and HO-I in Chang liver cells with a dose-effect response.

关 键 词：Chang肝细胞株 亚砷酸钠(NaAsO2) 转录因子Nrf2 血红素单加氧酶-1(HO-1) NAD(P)H:醌氧化还原酶1(NQO1) 

分 类 号：R135.99[医药卫生—劳动卫生]