文献类型：期刊文献

中文题名：Anti-aging effects of chlorpropamide depend on mitochondrial complex-Ⅱ and the production of mitochondrial reactive oxygen species

作者：Zhifan Mao[1];Wenwen Liu[1];Yunyuan Huang[1];Tianyue Sun[1];Keting Bao[1];Jiali Feng[1];Alexey Moskalev[2];Zelan Hu[1];Jian Li[1,3,4]

机构：[1]State Key Laboratory of Bioreactor Engineering,Frontiers Science Center for Materiobiology and Dynamic Chemistry,Shanghai Key Laboratory of New Drug Design,East China University of Science and Technology,Shanghai 200237,China;[2]Laboratory of Geroprotective and Radioprotective Technologies,Institute of Biology,Komi Science Centre,Ural Branch,Russian Academy of Sciences,Syktyvkar 167982,Russia;[3]Yunnan Key Laboratory of Screening and Research on Anti-pathogenic Plant Resources from West Yunnan,College of Pharmacy,Dali University,Dali 671000,China;[4]Clinical Medicine Scientific and Technical Innovation Center,Shanghai Tenth People’s Hospital,Tongji University School of Medicine,Shanghai 200092,China

年份：2022

卷号：12

期号：2

起止页码：665

中文期刊名：Acta Pharmaceutica Sinica B

外文期刊名：药学学报（英文版）

收录：CSTPCD;;Scopus;CSCD:【CSCD2021_2022】；PubMed;

基金：Financial support for this research provided by the National Natural Science Foundation of China(22037002 and 81772689);the Program for Professor of Special Appointment(Eastern Scholar TP2018025,China)at Shanghai Institutions of Higher Learning;the Innovative Research Team of High-level Local Universities in Shanghai;the Chinese Special Fund for State Key Laboratory of Bioreactor Engineering(2060204,China);Strains of Caenorhabditis elegans were provided by the CGC,which is funded by NIH Office of Research Infrastructure Programs(P40 OD010440)。

语种：英文

中文关键词：Sulfonylureas;Chlorpropamide;Anti-aging;Mitochondrial complexⅡ;Mitochondrial reactive oxygen species;ATP sensitive potassium channels;Senescence;Succinate dehydrogenase;

摘要：Sulfonylureas are widely used oral anti-diabetic drugs.However,its long-term usage effects on patients’lifespan remain controversial,with no reports of influence on animal longevity.Hence,the anti-aging effects of chlorpropamide along with glimepiride,glibenclamide,and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K+(mito K-ATP)channels and mitochondrial complex II.Chlorpropamide delayed aging in Caenorhabditis elegans,human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice.In addition,the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms,which is consistent with the function of its reported targets,mito K-ATP channels.Increased levels of mitochondrial reactive oxygen species(mt ROS)were observed in chlorpropamide-treated worms.Moreover,the lifespan extension by chlorpropamide required complex II and increased mt ROS levels,indicating that chlorpropamide acts on complex II directly or indirectly via mito K-ATP to increase the production of mt ROS as a pro-longevity signal.This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C.elegans.