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Inhibited peroxidase activity of peroxiredoxin 1 by palmitic acid exacerbates nonalcoholic steatohepatitis in male mice

文献类型：期刊论文

作者Yin, Wen10,11; Xu, Heng8,9; Bai, Zhonghao7,10,11; Wu, Yue6,8; Zhang, Yan10,11; Liu, Rui10,11; Wang, Zhangzhao10,11; Zhang, Bei6,8; Shen, Jing10,11; Zhang, Hao8,9
刊名NATURE COMMUNICATIONS
出版日期2025-01-11
卷号16期号:1页码:19
DOI10.1038/s41467-025-55939-2
英文摘要Reactive oxygen species exacerbate nonalcoholic steatohepatitis (NASH) by oxidizing macromolecules; yet how they promote NASH remains poorly understood. Here, we show that peroxidase activity of global hepatic peroxiredoxin (PRDX) is significantly decreased in NASH, and palmitic acid (PA) binds to PRDX1 and inhibits its peroxidase activity. Using three genetic models, we demonstrate that hepatic PRDX1 protects against NASH in male mice. Mechanistically, PRDX1 suppresses STAT signaling and protects mitochondrial function by scavenging hydrogen peroxide, and mitigating the oxidation of protein tyrosine phosphatases and lipid peroxidation. We further identify rosmarinic acid (RA) as a potent agonist of PRDX1. As revealed by the complex crystal structure, RA binds to PRDX1 and stabilizes its peroxidatic cysteine. RA alleviates NASH through specifically activating PRDX1's peroxidase activity. Thus, beyond revealing the molecular mechanism underlying PA promoting oxidative stress and NASH, our study suggests that boosting PRDX1's peroxidase activity is a promising intervention for treating NASH.
WOS关键词FATTY LIVER-DISEASE ; CYSTEINE SULFINIC ACID ; OXIDATIVE STRESS ; INSULIN SENSITIVITY ; INFLAMMATION ; NASH ; FIBROSIS ; OBESITY ; CELLS ; ACTIVATION
资助项目National Natural Science Foundation of China (National Science Foundation of China) ; National Centre for Protein Science Shanghai (Protein Expression and Purification system)[2019YFA0802500] ; National Centre for Protein Science Shanghai (Protein Expression and Purification system)[2021ZD0203900] ; National Centre for Protein Science Shanghai (Protein Expression and Purification system)[2022YFC3400500] ; National Key Research and Development Program of China[32271202] ; National Key Research and Development Program of China[31971076] ; National Key Research and Development Program of China[U23A20108] ; National Key Research and Development Program of China[92253303] ; National Key Research and Development Program of China[81821005] ; National Key Research and Development Program of China[91853205] ; National Key Research and Development Program of China[81903538] ; National Key Research and Development Program of China[82104064] ; National Natural Science Foundation of China[20JCJQJC00240] ; Tianjin Municipal Science and Technology Commission[19XD1404700] ; Science and Technology Commission of Shanghai Municipality[ZYYCXTD-202004] ; National Multidisciplinary Innovation Team of Traditional Chinese Medicine[2024XKNFM12] ; Discipline Research Special Project of Tianjin Medical University[GZNL2023A02012] ; R&D Program of Guangzhou National Laboratory[(XDB0830000] ; Chinese Academy of Sciences[TJYXZDXK-032A] ; Tianjin Key Medical Discipline (Specialty) Construction Project
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001396245300022
出版者NATURE PORTFOLIO
源URL[http://119.78.100.183/handle/2S10ELR8/315881]  
专题新药研究国家重点实验室
通讯作者Luo, Cheng; Xie, Xiangyang
作者单位1.Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Hangzhou 310053, Peoples R China
2.City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Peoples R China
3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
4.Tianjin Med Univ, Gen Hosp, Dept Pharm, Tianjin 300052, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Nutr & Hlth SINH, CAS Key Lab Nutr Metab & Food Safety Res, Shanghai, Peoples R China
6.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China
7.Tianjin Med Univ, Dept Immunol, Key Lab Immune Microenvironm & Dis, Minist Educ,NHC Key Lab Hormones & Dev, Tianjin 300070, Peoples R China
8.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
9.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310000, Peoples R China
10.Tianjin Med Univ, Tianjin Inst Endocrinol, Tianjin 300134, Peoples R China
推荐引用方式
GB/T 7714		 Yin, Wen,Xu, Heng,Bai, Zhonghao,et al. Inhibited peroxidase activity of peroxiredoxin 1 by palmitic acid exacerbates nonalcoholic steatohepatitis in male mice[J]. NATURE COMMUNICATIONS,2025,16(1):19.
APA Yin, Wen.,Xu, Heng.,Bai, Zhonghao.,Wu, Yue.,Zhang, Yan.,...&Xie, Xiangyang.(2025).Inhibited peroxidase activity of peroxiredoxin 1 by palmitic acid exacerbates nonalcoholic steatohepatitis in male mice.NATURE COMMUNICATIONS,16(1),19.
MLA Yin, Wen,et al."Inhibited peroxidase activity of peroxiredoxin 1 by palmitic acid exacerbates nonalcoholic steatohepatitis in male mice".NATURE COMMUNICATIONS 16.1(2025):19.

入库方式： OAI收割

来源：上海药物研究所

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