A potent PGK1 antagonist reveals PGK1 regulates the production of IL-1 beta and IL-6
文献类型：期刊论文
| 作者 | Liao, Liping3,4; Dang, Wenzhen1,2,3; Lin, Tingting3,4; Yu, Jinghua3; Liu, Tonghai3,4; Li, Wen3; Xiao, Senhao3,4; Feng, Lei3,4; Huang, Jing3,4; Fu, Rong3 |
| 刊名 | ACTA PHARMACEUTICA SINICA B
 |
| 出版日期 | 2022-11-01 |
| 卷号 | 12期号:11页码:4180-4192 |
| 关键词 | Glycolysis Phosphoglycerate kinase 1 Macrophages NRF2 Inflammation |
| ISSN号 | 2211-3835 |
| DOI | 10.1016/j.apsb.2022.05.012 |
| 通讯作者 | Zhou, Bing(zhoubing@simm.ac.cn) ; Shen, Xiaoyan(shxiaoy@fudan.edu.cn) ; Luo, Cheng(cluo@simm.ac.cn) |
| 英文摘要 | Glycolytic metabolism enzymes have been implicated in the immunometabolism field through changes in metabolic status. PGK1 is a catalytic enzyme in the glycolytic pathway. Here, we set up a high-throughput screen platform to identify PGK1 inhibitors. DC-PGKI is an ATP-competitive inhibitor of PGK1 with an affinity of K-d = 99.08 nmol/L. DC-PGKI stabilizes PGK1 in vitro and in vivo, and suppresses both glycolytic activity and the kinase function of PGK1. In addition, DC-PGK1 unveils that PGK1 regulates production of IL-1 beta and IL-6 in LPS-stimulated macrophages. Mechanistically, inhibition of PGK1 with DC-PGKI results in NRF2 (nuclear factor-erythroid factor 2related factor 2, NFE2L2) accumulation, then NRF2 translocates to the nucleus and binds to the proximity region of Il-1 beta and 11-6 genes, and inhibits LPS-induced expression of these genes. DC-PGK1 ameliorates colitis in the dextran sulfate sodium (DSS)-induced colitis mouse model. These data support PGK1 as a regulator of macrophages and suggest potential utility of PGK1 inhibitors in the treatment of inflammatory bowel disease. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. |
| WOS关键词 | CELL-PROLIFERATION ; CANCER ; GLYCOLYSIS ; METABOLISM ; KINASE ; MYC ; MACROPHAGES ; INHIBITION ; ITACONATE ; SUCCINATE |
| 资助项目 | National Key Research and Development Program of China[2021ZD0203900] ; National Natural Science Foundation of China[91853205] ; National Natural Science Foundation of China[81821005] ; Science and Technology Commission of Shanghai Municipality[19XD1404700] ; National Multidisciplinary Innovation Team of Traditional Chinese Medicine - National Administration of Traditional Chinese Medicine[LG-QS-202206-01] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000898383000001 |
| 出版者 | INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/304013]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhou, Bing; Shen, Xiaoyan; Luo, Cheng |
| 作者单位 | 1.Fudan Univ, Sch Pharm, Minist Educ, Dept Pharmacol, Shanghai 201203, Peoples R China 2.Fudan Univ, Sch Pharm, Key Lab Smart Drug Delivery, Minist Educ, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China 6.Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Hangzhou 310053, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liao, Liping,Dang, Wenzhen,Lin, Tingting,et al. A potent PGK1 antagonist reveals PGK1 regulates the production of IL-1 beta and IL-6[J]. ACTA PHARMACEUTICA SINICA B,2022,12(11):4180-4192. |
| APA | Liao, Liping.,Dang, Wenzhen.,Lin, Tingting.,Yu, Jinghua.,Liu, Tonghai.,...&Luo, Cheng.(2022).A potent PGK1 antagonist reveals PGK1 regulates the production of IL-1 beta and IL-6.ACTA PHARMACEUTICA SINICA B,12(11),4180-4192. |
| MLA | Liao, Liping,et al."A potent PGK1 antagonist reveals PGK1 regulates the production of IL-1 beta and IL-6".ACTA PHARMACEUTICA SINICA B 12.11(2022):4180-4192. |
入库方式： OAI收割
来源：上海药物研究所
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