SUMO特异性蛋白酶1对hPXR调控P-gp基因表达的影响  

Effects of SUMO specific protease 1 on h PXR-mediated P-gp gene expression

作　　者：李樱媚 许晨舒[1] 黎张燕 陈孝[1] 

机构地区：[1]中山大学附属第一医院药学部,广东广州510080

出　　处：《药学学报》2015年第9期1192-1196,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81402998)

摘　　要：孕烷X受体（pregnane X receptor,PXR）属于核受体（nuclear receptors,NRs）超家族的一员,是一个配体依赖性的转录调节因子[1]。配体激活后的PXR进入细胞核,与视黄醛X受体（retinoid X receptor,RXR）形成异二聚体,随后结合到靶基因的PXR反应元件上,进而介导该基因的转录表达。PXR下游靶基因的表达产物主要是一类与外源性药物及内源性物质代谢转运相关的酶及蛋白，包括I相代谢酶如细胞色素P450同工酶家族中的CYP3A、CYP2B和CYP2C。II相代谢酶如尿苷二磷酸葡萄糖醛酸转移酶基因（UGT）和谷胱甘肽S转移酶（GST），III相药物转运蛋白如P-糖蛋白（p-gP）、多药耐药相关蛋白（MRP）和乳腺癌耐药蛋白（BCRP）等。The study aimed to investigate the effects of small ubiquitin-related modifier（SUMO） specific protease 1（SENP1） on human PXR-mediated MDR1 transcriptional activity and m RNA expression. Empty vector and expression plasmids, including PXR, SENP1 and SENP1 mutant（SENP1m） were transiently transfected into Hep G2 and LS174 T cells using Lipo2000. Transcriptional activity was detected by dual luciferase reporter gene assay, and m RNA level was measured using real-time polymerase chain reaction. The results showed that SENP1 could remarkably reduce the rifampicin（RIF）-induced MDR1 reporter activity and m RNA level in h PXR over expressed Hep G2 and LS174 T cells（P〈0.05）, whereas adding SENP1 m restored the RIF-induced increases（P〈0.05）. These results indicated that SENP1 could repress the RIF-induced h PXR-mediated MDR1 transcriptional activity and m RNA expression.

关 键 词：孕烷X受体 P-糖蛋白 小类泛素化蛋白 SUMO特异性蛋白酶1 

分 类 号：R966[医药卫生—药理学]