論文 - 詳細
| RRC ID | 51883 |
|---|---|
| 著者 | Wu WJ, Jia WW, Liu XH, Pan LL, Zhang QY, Yang D, Shen XY, Liu L, Zhu YZ. |
| タイトル | S-propargyl-cysteine attenuates inflammatory response in rheumatoid arthritis by modulating the Nrf2-ARE signaling pathway. |
| ジャーナル | Redox Biol |
| Abstract |
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder. Hydrogen sulfide (H2S), the third physiological gasotransmitter, is well recognized as an anti-inflammatory mediator in various inflammatory conditions. Herein, we explored the protective effects of S-propargyl-cysteine (SPRC, also known as ZYZ-802), an endogenous H2S modulator, on RA and determined the underlying mechanisms. In the present study, SPRC concentration-dependently attenuated inflammatory mediator expression, reactive oxidase species generation, and the expression and activity of matrix metalloproteinases (MMP)-9 in interleukin (IL)-1β-induced human rheumatoid fibroblast-like synoviocytes MH7A. In addition, SPRC blocked IL-1β-mediated migration and invasion of MH7A cells. As expected, the protective effects of SPRC were partially abrogated by DL-propargylglycine (PAG, a H2S biosynthesis inhibitor). In vivo study also demonstrated that SPRC treatment markedly ameliorated the severity of RA in adjuvant-induced arthritis rats, and this effect was associated with the inhibition of inflammatory response. We further identified that SPRC remarkably induced heme oxygenase-1 expression associated with the degradation of Kelch-like ECH-associated protein 1 (Keap1) and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2); this effect was attributed to the sulfhydrylation of the cysteine residue of Keap1. Our data demonstrated for the first time that SPRC, an endogenous H2S modulator, exerted anti-inflammatory properties in RA by upregulating the Nrf2-antioxidant response element (ARE) signaling pathway. |
| 巻・号 | 10 |
| ページ | 157-167 |
| 公開日 | 2016-12-1 |
| DOI | 10.1016/j.redox.2016.08.011 |
| PII | S2213-2317(16)30122-7 |
| PMID | 27744121 |
| PMC | PMC5066299 |
| MeSH | Animals Anti-Inflammatory Agents / administration & dosage* Anti-Inflammatory Agents / pharmacology Antioxidant Response Elements / drug effects* Arthritis, Rheumatoid / drug therapy* Arthritis, Rheumatoid / genetics Cell Line Cell Movement / drug effects Cell Survival Cysteine / administration & dosage Cysteine / analogs & derivatives* Cysteine / pharmacology Disease Models, Animal Dose-Response Relationship, Drug Humans Male NF-E2-Related Factor 2 / genetics* Rats Rats, Sprague-Dawley Reactive Oxygen Species / metabolism Signal Transduction / drug effects Up-Regulation |
| IF | 9.986 |
| 引用数 | 23 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MH7A(RCB1512) |