亚砷酸钠对胰岛β细胞的Nrf2及其调控的抗氧化酶表达的影响

摘要

目的 检测亚砷酸钠对小鼠胰岛β细胞的核转录因子Nrf2及其调控的抗氧化酶硫氧还蛋白(Srx),γ-谷氨酰半胱氨酸连接酶催化亚基(Gclc)表达的影响.方法 应用2、4、6、8、10μmol/L亚砷酸钠(NaAsO2)作用MIN6细胞6h,通过Western Blot检测Nrf2蛋白表达；利用Real-time PCR检测抗氧化酶Srx、Gclc的mRNA表达.结果 4μmol/L亚砷酸钠染毒6h后,Nrf2的蛋白表达显著增高,并随着亚砷酸钠剂量的增大,Nrf2蛋白表达也随之增多.抗氧化酶Srx、Gclc mRNA在2μmol/L亚砷酸钠染毒6h后开始出现明显的诱导表达,并随亚砷酸钠剂量的增加而表达增强.结论 亚砷酸钠能诱导小鼠胰岛β细胞Nrf2蛋白及其调控的抗氧化酶Srx和Gclc基因的表达,并存在显著地剂量依赖性.%Objective To investigate the expressions of Nrf2 and its regulated downstream antioxidases induced by sodium arsenite (NaAsO2) in mouse pancreatic β-cell MIN6. Methods MIN6 cells were exposed to control(medium) or 2, 4, 6, 8,10μmol/L NaAsO2 for 6h. The protein expression of Nrf2 was detected by Western Blot. The mRNA expressions of antioxidases were measured by Real-time PCR. Results The protein level of Nrf2 was significantly increased by 4, 6, 8, 10μmol/L NaAsO2 for 6h. The induction of some antioxidant genes, including sulfiredoxin (Srx) and γ-glutamate cysteine ligase catalytic subunit (Gclc), was markedly enhanced in a dose-dependent fashion. Conclusion The expressions of Nrf2 and its regulated downstream antioxidases Srx and Gclc can be induced dose-dependently by sodium arsenite in mousue pancreatic β-cell MIN6.