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Sulfasalazine promotes ferroptosis through AKT-ERK1/2 and P53-SLC7A11 in rheumatoid arthritis

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机构: [1]Department of Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, 29 Xinglong Alley, Changzhou, 213003, China. [2]Graduate School of Dalian Medical University, 9 West Section, Shunnan Road, Dalian, 116044, China. [3]Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, 210039, China. [4]Truma Central, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, 29 Xinglong Alley, Changzhou, 213003, China. [5]Department of Orthopedics, Affiliated Sport Hospital of CDSU (Chengdu Sport University), 251 Wuhouci Street, Chengdu, 610041, China. [6]Department of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA. [7]Medical Research Center, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, 29 Xinglong Alley, Changzhou, 213003, China. [8]Guangdong Provincial Key Laboratory of Genome Stability and Disease Prevention, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, 518055, People's Republic of China. [9]Department of Orthopedics, The Third Affiliated Hospital of Gansu University of Chinese Medicine, 222 Silong Road, Baiyin, 730900, China
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关键词: Ferroptosis Rheumatoid arthritis Sulfasalazine Fibroblast-like synoviocyte

摘要:
Ferroptosis has been reported to play a role in rheumatoid arthritis (RA). Sulfasalazine, a common clinical treatment for ankylosing spondylitis, also exerts pathological influence on the progression of rheumatoid arthritis including the induced ferroptosis of fibroblast-like synoviocytes (FLSs), which result in the perturbated downstream signaling and the development of RA. The aim of this study was to investigate the underlying mechanism so as to provide novel insight for the treatment of RA.CCK-8 and Western blotting were used to assess the effect of sulfasalazine on FLSs. A collagen-induced arthritis mouse model was constructed by the injection of collagen and Freund's adjuvant, and then, mice were treated with sulfasalazine from day 21 after modeling. The synovium was extracted and ferroptosis was assessed by Western blotting and immunofluorescence staining.The results revealed that sulfasalazine promotes ferroptosis. Compared with the control group, the expression levels of ferroptosis-related proteins such as glutathione peroxidase 4, ferritin heavy chain 1, and solute carrier family 7, member 11 (SLC7A11) were lower in the experimental group. Furthermore, deferoxamine inhibited ferroptosis induced by sulfasalazine. Sulfasalazine-promoted ferroptosis was related to a decrease in ERK1/2 and the increase of P53.Sulfasalazine promoted ferroptosis of FLSs in rheumatoid arthritis, and the PI3K-AKT-ERK1/2 pathway and P53-SLC7A11 pathway play an important role in this process.© 2024. The Author(s).

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出版当年[2023]版:
大类 | 2 区 医学
小类 | 1 区 毒理学 3 区 免疫学
最新[2025]版:
大类 | 3 区 医学
小类 | 2 区 毒理学 3 区 免疫学
第一作者:
第一作者机构: [1]Department of Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, 29 Xinglong Alley, Changzhou, 213003, China. [2]Graduate School of Dalian Medical University, 9 West Section, Shunnan Road, Dalian, 116044, China.
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通讯机构: [1]Department of Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, 29 Xinglong Alley, Changzhou, 213003, China. [6]Department of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA. [9]Department of Orthopedics, The Third Affiliated Hospital of Gansu University of Chinese Medicine, 222 Silong Road, Baiyin, 730900, China
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