毒杀芬对孤儿受体雌激素相关受体1(ERRα-1)的拮抗作用  

The antagonists of ERRα-1 orphan receptor: toxaphene

作　　者：杨春[1] 陈彬[1] 陈敏[1] 陈健[1] 李渝萍[1] 周长保[1] 周度金[1] 陈煊 

机构地区：[1]第三军医大学基础医学部生物化学与分子生物学教研室,重庆400038 [2]Beckman Research Institute of the City of Hope

出　　处：《第三军医大学学报》2001年第10期1183-1185,共3页Journal of Third Military Medical University

基　　金：国家自然科学基金资助项目 ( 30 0 70 2 35 9)

摘　　要：目的　研究毒杀芬 (Toxaphene)对孤儿受体雌激素相关受体 1 (Estrogen relatedreceptor,ERRα 1 )活性的影响。方法　细胞瞬时和稳定转染及氯霉素酰基转移酶和芳香族化酶活性测定。结果　毒杀芬抑制了由ERRα 1所介导的氯霉素酰基转移酶的转录表达和辅活化子 (Coactivator)GRIP1诱导的ERRα 1的活性。在构建的稳定高表达ERRα 1的HepG2肝癌细胞株中 ,ERRα 1增加了芳香族化酶的转录表达 ,ERRα 1高表达细胞株与 1 0 μmol/L浓度的毒杀芬温育 2 4h后 ,芳香族化酶活性降低到非ERRα 1转染的HepG2细胞中芳香族化酶活性的水平。结论　毒杀芬是ERRα 1的拮抗剂 ,它拮抗了ERRα 1调节芳香族化酶转录的作用 ,从而使该酶的表达量降低。Objective To explore the effect of toxaphene on the activity of orphan nuclear receptor, estrogen related receptor α 1 (ERRα 1). Methods Transient and stable transfection experiments in cells and assays of chloramphenicol acetyltransferase activity and aromatase activity were used. Results Toxaphene had an antagonist activity against ERRα 1 mediated transcription of the reporter chloramphenicol acetyltransferase (CAT) and to be capable of suppressing the GRIP1 coactivator induced ERRα 1 activity as revealed by transient transfection experiments using the SK BR 3 breast cancer cell line. In addition. A stable ERRα 1 expressing HepG2 hepatoma cell line was generated, and the aromatase activity in the transfected cell line was found to be twice that in the untransfected cell line. 24 h incubation of an ERRα 1 transfected HepG2 cell line with 10 μmol/L toxaphene reduced its aromatase activity to the level in the untransfected cell line. Conclusion Toxaphene is the antagonist of ERRα 1. It antagonize the regulation of aromatase activity and decrease the expression of aromatase.

关 键 词：雌激素相关受体 毒杀芬 孤儿受体 芳香族化酶 

分 类 号：R979.8[医药卫生—药品]