Nrf2通路在氟他胺诱导的肝细胞线粒体生物合成中的作用  

Role of Nrf2 pathway in flutamide-induced mitochondrial biogenesis

作　　者：张丽 王进 李惠子 彭辉 何俊 彭双清 郭家彬 ZHANG Li;WANG Jin;LI Huizi;PENG Hui;HE Jun;PENG Shuangqing;GUO Jiabin(Chinese PLA Center for Disease Control and Prevention,Beijing 100071,China;Chinese PLA Rocket Force Characteristic Medical Center,Beijing 100120,China)

机构地区：[1]中国人民解放军疾病预防控制中心,北京100071 [2]火箭军特色医学中心,北京100120

出　　处：《中国临床药理学与治疗学》2022年第5期498-504,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金项目(81973407);国家自然科学基金项目(81430090)。

摘　　要：目的:探讨氟他胺对人肝细胞线粒体生物合成的影响以及抗氧化通路Nrf2的调节作用。方法:采用人源肝细胞HepG2,氟他胺(0~50μmol/L)给药24 h,通过RT-PCR和Western blot方法,检测mtDNA拷贝数和线粒体生物合成关键蛋白的表达,再通过应用基因敲降和特异性激活剂或抑制剂等技术方法进一步观察ERK1/2对氟他胺诱导的线粒体生物合成的影响以及Nrf2通路的调控作用。结果:氟他胺可诱导线粒体生物合成,mtDNA拷贝数和ERK1/2、PGC-1α蛋白均呈现剂量依赖性上升;ERK1/2抑制和激活能改变氟他胺诱导的mtDNA拷贝数和PGC-1α的表达;Nrf2通路抑制可影响氟他胺诱导的mtDNA拷贝数和ERK1/2、PGC-1α的表达。结论:氟他胺可影响线粒体生物合成,其机制与Nrf2介导的ERK1/2改变密切相关。AIM:To investigate the effect of flutamide on mitochondrial biogenesis and the regulating effect of anoxidative pathway Nrf2 on it.METHODS:Human hepatocyte HepG2 cells were treated with flutamide(0-50μmol/L)for 24 h,then mtDNA copy number and protein expression of mitochondrial biogenesis were detected by RT-PCR and WB.The effects of ERK1/2 and the role of Nrf2 pathway in mitochondrial biogenesis were further observed by gene knockdown and protein activation/inhibition methods.RESULTS:Flutamide interfered mitochondrial biogenesis concentration-dependently,the mtDNA copy number,ERK1/2 and PGC-1αproteins increased with the dose.ERK1/2 inhibition and activation regulated flutamide-induced mtDNA copy number and PGC-1αexpression,and inhibition of Nrf2 pathway also affected flutamide-induced mtDNA copy number and expression of PGC-1α,as well as ERK1/2 expression.CONCLUSION:Flutamide affects mitochondrial biogenesis,and the antioxidant pathway Nrf2 may be involved in the regulation of flutamine-induced mitochondrial biogenesis by regulating ERK1/2.

关 键 词：线粒体生物合成 氟他胺 NRF2 ERK1/2 PGC-1Α 

分 类 号：R965.2[医药卫生—药理学]