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7-aminocephalosporanic acid, a novel HSP90 beta inhibitor, attenuates HFD-induced hepatic steatosis

文献类型：期刊论文

作者Zhang, Weitao4,5; Xue, Hanyue5; Zhou, Chen1,3; Zheng, Zuguo5; Xing, Mingming5; Chu, Hang5; Li, Ping5; Zhang, Naixia1,3; Dang, Yongjun2; Xu, Xiaojun4,5
刊名BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
出版日期2022-09-24
卷号622页码:184-191
ISSN号0006-291X
关键词7-aminocephalosporanic acid HSP90 beta NAFLD de novo lipogenesis SPR
DOI10.1016/j.bbrc.2022.07.033
通讯作者Xu, Xiaojun(xiaojunxu@cpu.edu.cn)
英文摘要Hepatic steatosis is one of the most important causes of liver disease worldwide. Heat shock protein 90 (HSP90) is essential for numerous client proteins. Recently, more attention was focused on increased HSP90 levels in hepatic steatosis, especially HSP90 beta. Thus, great efforts have been made to develop HSP90 beta inhibitors, and most natural inhibitors are derived from microorganisms. In this study, using microarray chips and surface pasmon resonance (SPR) technology, we screened 189 antibiotics in order to obtain an inhibitor directly binding to the non-N-terminal domain of HSP90 beta. Finally, we discovered an antibiotic, 7-aminocephalosporanic acid (7ACA), with a K-D value of 6.201 mu M between 7ACA and non-N-terminal domain of HSP90 beta. Besides, 7ACA was predicted to interact with the middle domain (MD) of HSP90 beta. In HepG2 cells, we found that 7ACA reduced cellular total cholesterol (TC) and triglyceride (TG) by decreasing sterol regulatory element-binding proteins (SREBPs). In HFD fed mice, administration of 7ACA (5, 10, and 25 mg kg(-1) d(-1), ig, for 12 weeks) dose-dependently decreased serum TC and TG and played an important role in protecting liver and adipose tissue from lipid accumulation. In conclusion, our study demonstrated that antibiotic 7ACA, as an HSP90 beta middle domain inhibitor, was promising for the development of lipid-lowering drugs. (C) 2022 Elsevier Inc. All rights reserved.
WOS关键词PROTEIN CHAPERONE ; TERMINAL DOMAIN ; ANSAMYCINS ; NOVOBIOCIN ; RADICICOL ; ACYLASE
资助项目National Science Foundation of China[81773957] ; National Science and Technology Major Projects for Major New Drugs Innovation and Development[2019ZX09201001-001-001] ; Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University[SKLNMZZCX201820]
WOS研究方向Biochemistry & Molecular Biology ; Biophysics
语种英语
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号WOS:000878146800011
源URL[http://119.78.100.183/handle/2S10ELR8/303029]  
专题中国科学院上海药物研究所
通讯作者Xu, Xiaojun
作者单位1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
2.Chongqing Med Univ, Ctr Novel Target & Therapeut Intervent, Inst Life Sci, Chongqing 400016, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China
4.China Pharmaceut Univ, Jiangsu Key Lab Drug Discovery Metab Dis, Nanjing 210009, Jiangsu, Peoples R China
5.China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Weitao,Xue, Hanyue,Zhou, Chen,et al. 7-aminocephalosporanic acid, a novel HSP90 beta inhibitor, attenuates HFD-induced hepatic steatosis[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2022,622:184-191.
APA Zhang, Weitao.,Xue, Hanyue.,Zhou, Chen.,Zheng, Zuguo.,Xing, Mingming.,...&Xu, Xiaojun.(2022).7-aminocephalosporanic acid, a novel HSP90 beta inhibitor, attenuates HFD-induced hepatic steatosis.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,622,184-191.
MLA Zhang, Weitao,et al."7-aminocephalosporanic acid, a novel HSP90 beta inhibitor, attenuates HFD-induced hepatic steatosis".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 622(2022):184-191.

入库方式： OAI收割

来源：上海药物研究所

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