S-propargyl-cysteine attenuates inflammatory response in rheumatoid arthritis by modulating the Nrf2-ARE signaling pathway
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,...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-12-01
|
| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231716301227 |
| _version_ | 1828522381127188480 |
|---|---|
| author | Wei-Jun Wu Wan-Wan Jia Xin-Hua Liu Li-Long Pan Qiu-Yan Zhang Di Yang Xiao-Yan Shen Liang Liu Yi Zhun Zhu |
| author_facet | Wei-Jun Wu Wan-Wan Jia Xin-Hua Liu Li-Long Pan Qiu-Yan Zhang Di Yang Xiao-Yan Shen Liang Liu Yi Zhun Zhu |
| author_sort | Wei-Jun Wu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T20:06:48Z |
| format | Article |
| id | doaj.art-556daf5e5a91472dbd7de6ad807bb189 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-11T20:06:48Z |
| publishDate | 2016-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-556daf5e5a91472dbd7de6ad807bb1892022-12-22T00:52:23ZengElsevierRedox Biology2213-23172016-12-0110C15716710.1016/j.redox.2016.08.011S-propargyl-cysteine attenuates inflammatory response in rheumatoid arthritis by modulating the Nrf2-ARE signaling pathwayWei-Jun Wu0Wan-Wan Jia1Xin-Hua Liu2Li-Long Pan3Qiu-Yan Zhang4Di Yang5Xiao-Yan Shen6Liang Liu7Yi Zhun Zhu8Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, ChinaShanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, ChinaShanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, ChinaShanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, ChinaShanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, ChinaShanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, ChinaShanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, ChinaState Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology, Macau, ChinaShanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, ChinaRheumatoid 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.http://www.sciencedirect.com/science/article/pii/S2213231716301227S-propargyl-cysteineArthritisCystathionine γ-synthaseNuclear factor erythroid-2-related factor 2 |
| spellingShingle | Wei-Jun Wu Wan-Wan Jia Xin-Hua Liu Li-Long Pan Qiu-Yan Zhang Di Yang Xiao-Yan Shen Liang Liu Yi Zhun Zhu S-propargyl-cysteine attenuates inflammatory response in rheumatoid arthritis by modulating the Nrf2-ARE signaling pathway Redox Biology S-propargyl-cysteine Arthritis Cystathionine γ-synthase Nuclear factor erythroid-2-related factor 2 |
| title | S-propargyl-cysteine attenuates inflammatory response in rheumatoid arthritis by modulating the Nrf2-ARE signaling pathway |
| title_full | S-propargyl-cysteine attenuates inflammatory response in rheumatoid arthritis by modulating the Nrf2-ARE signaling pathway |
| title_fullStr | S-propargyl-cysteine attenuates inflammatory response in rheumatoid arthritis by modulating the Nrf2-ARE signaling pathway |
| title_full_unstemmed | S-propargyl-cysteine attenuates inflammatory response in rheumatoid arthritis by modulating the Nrf2-ARE signaling pathway |
| title_short | S-propargyl-cysteine attenuates inflammatory response in rheumatoid arthritis by modulating the Nrf2-ARE signaling pathway |
| title_sort | s propargyl cysteine attenuates inflammatory response in rheumatoid arthritis by modulating the nrf2 are signaling pathway |
| topic | S-propargyl-cysteine Arthritis Cystathionine γ-synthase Nuclear factor erythroid-2-related factor 2 |
| url | http://www.sciencedirect.com/science/article/pii/S2213231716301227 |
| work_keys_str_mv | AT weijunwu spropargylcysteineattenuatesinflammatoryresponseinrheumatoidarthritisbymodulatingthenrf2aresignalingpathway AT wanwanjia spropargylcysteineattenuatesinflammatoryresponseinrheumatoidarthritisbymodulatingthenrf2aresignalingpathway AT xinhualiu spropargylcysteineattenuatesinflammatoryresponseinrheumatoidarthritisbymodulatingthenrf2aresignalingpathway AT lilongpan spropargylcysteineattenuatesinflammatoryresponseinrheumatoidarthritisbymodulatingthenrf2aresignalingpathway AT qiuyanzhang spropargylcysteineattenuatesinflammatoryresponseinrheumatoidarthritisbymodulatingthenrf2aresignalingpathway AT diyang spropargylcysteineattenuatesinflammatoryresponseinrheumatoidarthritisbymodulatingthenrf2aresignalingpathway AT xiaoyanshen spropargylcysteineattenuatesinflammatoryresponseinrheumatoidarthritisbymodulatingthenrf2aresignalingpathway AT liangliu spropargylcysteineattenuatesinflammatoryresponseinrheumatoidarthritisbymodulatingthenrf2aresignalingpathway AT yizhunzhu spropargylcysteineattenuatesinflammatoryresponseinrheumatoidarthritisbymodulatingthenrf2aresignalingpathway |