PRDX1 Cys52Ser variant alleviates nonalcoholic steatohepatitis by reducing inflammation in mice
文献类型：期刊论文
| 作者 | Bai, Zhonghao4,5; Yin, Wen4,5; Liu, Rui4,5; Tang, Minglei4,5; Shi, Xiaokeng4,5; Luo, Cheng2,3 ; Xie, Xiangyang1,4,5
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| 刊名 | MOLECULAR METABOLISM
 |
| 出版日期 | 2023-10-01 |
| 卷号 | 76页码:9 |
| ISSN号 | 2212-8778 |
| 关键词 | PRDX1 NASH Inflammation Cys52 NF-KB STAT1 |
| DOI | 10.1016/j.molmet.2023.101789 |
| 通讯作者 | Xie, Xiangyang(xyxie@tmu.edu.cn) |
| 英文摘要 | Objective: Peroxiredoxin 1 (PRDX1) is a peroxidase and guards against oxidative stress by scavenging intracellular peroxides, whereas it also has been shown to stimulate inflammatory response by functioning as a chaperone protein. The potential in vivo link between PRDX1's peroxidase activity and its pro-inflammatory activity remains elusive.Methods: We generated peroxidase-dead PRDX1 variant mice by mutating its peroxidatic cysteine at 52 (Cys52) to serine, here referred to as PRDX1Cys52Ser. Trx-TrxR-NADPH coupled activity assay was applied to evaluate the peroxidase activity of global PRDX in PRDX1Cys52Ser variant mice. PRDX1Cys52Ser mice and their wild-type littermates were subjected to western diet or methionine and choline deficient diet feeding. NASH phenotypes were assessed through different analyses including physiological measurements, immunohistochemical staining, and quantitative PCR (qPCR). RNA sequencing, qPCR and western blotting were used to reveal and validate any changes in the signaling pathways responsible for the altered NASH phenotypes observed between WT and PRDX1Cys52Ser variant mice.Results: PRDX1Cys52Ser variant mice showed impaired global PRDX peroxidase activity and reduced susceptibility to diet-induced NASH and liver fibrosis. Mechanistically, PRDX1 Cys52Ser variant suppressed NF -KB signaling and STAT1 signaling pathways that are known to promote inflammation and NASH.Conclusion: The peroxidatic Cys52 of PRDX1 is required for its pro-inflammatory activity in vivo. This study further suggests that PRDX1 may dual but roles in NASH. |
| WOS关键词 | OXIDATIVE STRESS ; PEROXIREDOXINS ; REDUCTASE ; DISEASE ; FAMILY |
| 资助项目 | National Key Research and Development Program of China[2019YFA0802500] ; National Natural Science Foundation of China[31971076] ; National Natural Science Foundation of China[32271202] ; Tianjin Municipal Science and Technology Commission[20JCJQJC00240] ; Tianjin Key Medical Discipline (Specialty) Construction Project[TJYXZDXK-032A] |
| WOS研究方向 | Endocrinology & Metabolism |
| 语种 | 英语 |
| 出版者 | ELSEVIER |
| WOS记录号 | WOS:001091172300001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/307542]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xie, Xiangyang |
| 作者单位 | 1.6 North Huanrui Rd, Tianjin 300134, Peoples R China 2.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310000, Peoples R China 3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528437, Peoples R China 4.Tianjin Med Univ, Tianjin Inst Endocrinol, Tianjin 300134, Peoples R China 5.Tianjin Med Univ, NHC Key Lab Hormones & Dev, Tianjin Key Lab Metab Dis, Chu Hsien I Mem Hosp, Tianjin 300134, Peoples R China |
| 推荐引用方式 GB/T 7714 | Bai, Zhonghao,Yin, Wen,Liu, Rui,et al. PRDX1 Cys52Ser variant alleviates nonalcoholic steatohepatitis by reducing inflammation in mice[J]. MOLECULAR METABOLISM,2023,76:9. |
| APA | Bai, Zhonghao.,Yin, Wen.,Liu, Rui.,Tang, Minglei.,Shi, Xiaokeng.,...&Xie, Xiangyang.(2023).PRDX1 Cys52Ser variant alleviates nonalcoholic steatohepatitis by reducing inflammation in mice.MOLECULAR METABOLISM,76,9. |
| MLA | Bai, Zhonghao,et al."PRDX1 Cys52Ser variant alleviates nonalcoholic steatohepatitis by reducing inflammation in mice".MOLECULAR METABOLISM 76(2023):9. |
入库方式： OAI收割
来源：上海药物研究所
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