• Login / Register
    View Item 
    •   Home
    • Faculty of Medicine, Dentistry and Life Sciences
    • Chester Medical School
    • Chester Medical School
    • View Item
    •   Home
    • Faculty of Medicine, Dentistry and Life Sciences
    • Chester Medical School
    • Chester Medical School
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChesterRepCommunitiesTitleAuthorsPublication DateSubmit DateSubjectsPublisherJournalThis CollectionTitleAuthorsPublication DateSubmit DateSubjectsPublisherJournalProfilesView

    My Account

    LoginRegister

    About

    AboutUniversity of Chester

    Statistics

    Display statistics

    Ca2+ signalling plays a role in celastrol-mediated suppression of synovial fibroblasts of rheumatoid arthritis patients and experimental arthritis in rats

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Wong, Vincent K-W.
    Qiu, Congling
    Xu, Su-Wei
    Law, Betty Yuen Kwan
    Zeng, Wu
    Wang, Hui
    Michelangeli, Francesco
    Dias, Ivo Ricardo De Seabra Rodrigues
    Qu, Yuan Qing
    Chan, Tsz Wai
    Han, Yu
    Zhang, Ni
    Mok, Simon Wing Fai
    Chen, Xi
    Yu, Lu
    Pan, Hudan
    Hamdoun, Sami
    Efferth, Thomas
    Yu, Wen Jing
    Zhang, Wei
    Li, Zheng
    Xie, Yuesheng
    Luo, Riqiang
    Jiang, Quan
    Liu, Liang
    Show allShow less
    Publication Date
    2019-05-23
    Submitted date
    2018-07-24
    
    Metadata
    Show full item record
    Abstract
    Celastrol exhibits anti-arthritic effect in rheumatoid arthritis (RA), but the role of celastrol-mediated Ca mobilization in treatment of RA remains unelucidated. Here, we illustrate the regulatory role of celastrol-induced Ca signalling in synovial fibroblasts of RA patients and adjuvant-induced arthritis (AIA) in rats. Molecular target of celastrol was determined by computational docking, Ca dynamic and functional assays on SERCA. Ca -mediated autophagy in RASFs/RAFLS and the underlying mechanism were verified by quantification of endogenous LC3-II puncta, immunoblotting, and flow cytometry with the Ca chelator (BAPTA/AM) or suitable inhibitors. The anti-arthritic effect of celastrol, autophagy induction and growth rate of synovial fibroblasts in AIA rats were monitored by microCT and immunofluorescence staining. mRNA from joint tissues of AIA rats was isolated for transcriptional analysis of inflammatory genes. The role of Ca in regulating the identified genes was investigated by knockdown of calmodulin, calpains, and calcineurin. Celastrol inhibited SERCA to induce autophagy-dependent cytotoxicity in RASFs/RAFLS via CaMKKβ-AMPK-mTOR pathway and repressed arthritis symptoms in AIA rats. BAPTA/AM hampered the in vitro and in vivo effectiveness of celastrol. Inflammatory- and autoimmunity-associated genes downregulated by celastrol in joint tissues of AIA rat were restored by BAPTA/AM. Knockdown of calmodulin, calpains, and calcineurin in RAFLS confirmed the role of Ca in celastrol-regulated gene expression. Celastrol triggered Ca signalling to induce autophagic cell death in RASFs/RAFLS and ameliorated arthritis in AIA rats mediated by calcium-dependent/-binding proteins facilitating the exploitation of anti-arthritic drugs based on manipulation of Ca signalling. [Abstract copyright: This article is protected by copyright. All rights reserved.]
    Citation
    British journal of pharmacology
    URI
    http://hdl.handle.net/10034/622333
    Type
    article
    Description
    From PubMed via Jisc Publications Router
    History: received 2018-07-24, revised 2019-05-04, accepted 2019-05-12
    Publication status: aheadofprint
    Collections
    Chester Medical School

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.