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The rheumatoid arthritis shared epitope increases cellular susceptibility to oxidative stress by antagonizing an adenosine-mediated anti-oxidative pathway
Ling, Song; Li, Zhanguo; Borschukova, Olga; Xiao, Liqun; Pumpens, Paul; Holoshitz, Joseph
刊名ARTHRITIS RESEARCH & THERAPY
2007
DOI10.1186/ar2111
9期:1
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Rheumatology
研究领域[WOS]Rheumatology
关键词[WOS]NITRIC-OXIDE ; DNA-DAMAGE ; GENOPROTECTIVE PATHWAYS ; ENDOTHELIAL-CELLS ; HYDROGEN-PEROXIDE ; T-CELLS ; ATTENUATION ; HEPATITIS ; ALLELES ; CAMP
英文摘要

We have recently demonstrated that the rheumatoid arthritis ( RA) shared epitope ( SE) acts as a ligand that triggers nitric oxide ( NO) signaling in opposite cells. Given the known prooxidative effect of NO and the proposed role of oxidative stress in the pathogenesis of RA, this study explores whether SE-triggered signaling can increase cellular oxidative stress. cAMP levels, adenylyl cyclase activity, and protein kinase A activity were measured using commercial kits. Generation of reactive oxygen species (ROS) was quantified using the fluorochrome dichlorofluorescein diacetate. Oxidative DNA damage was quantified using the single-cell electrophoresis technique. Here, we report that cells exposed to cell surface SE-positive HLA-DR ( human leukocyte antigen-DR) molecules, to cell-free recombinant proteins genetically engineered to express the SE motif, or to SE-positive synthetic peptide showed diminished cAMP-dependent signaling, increased ROS levels, and higher vulnerability to oxidative DNA damage. Introduction of single amino acid substitutions into SE-positive peptides revealed a consensus five-amino acid sequence motif of Q/R-K/R-X-X-A that is necessary and sufficient for SE-triggered signaling. The pro-oxidative effect of the SE could be reversed by inhibiting NO production. We conclude that the SE acts as a signaling ligand that activates an NO-mediated pro-oxidative pathway. The potential contribution of this signaling aberration to RA pathogenesis is discussed.

语种英语
WOS记录号WOS:000246250800011
引用统计
被引频次:26[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63591
专题北京大学第二临床医学院_风湿免疫科
作者单位1.Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA
2.Beijing Med Univ, Dept Rheumatol, Beijing 100044, Peoples R China
3.Latvian State Univ, Biomed Res & Study Ctr, LV-1067 Riga, Latvia
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GB/T 7714
Ling, Song,Li, Zhanguo,Borschukova, Olga,et al. The rheumatoid arthritis shared epitope increases cellular susceptibility to oxidative stress by antagonizing an adenosine-mediated anti-oxidative pathway[J]. ARTHRITIS RESEARCH & THERAPY,2007,9(1).
APA Ling, Song,Li, Zhanguo,Borschukova, Olga,Xiao, Liqun,Pumpens, Paul,&Holoshitz, Joseph.(2007).The rheumatoid arthritis shared epitope increases cellular susceptibility to oxidative stress by antagonizing an adenosine-mediated anti-oxidative pathway.ARTHRITIS RESEARCH & THERAPY,9(1).
MLA Ling, Song,et al."The rheumatoid arthritis shared epitope increases cellular susceptibility to oxidative stress by antagonizing an adenosine-mediated anti-oxidative pathway".ARTHRITIS RESEARCH & THERAPY 9.1(2007).
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