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p53 Contributes to Quercetin-Induced Apoptosis in Human Rheumatoid Arthritis Fibroblast-like Synoviocytes

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Abstract

In the present study, we sought to explore the mechanism of quercetin-induced apoptosis in rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs). DNA fragmentation assay was used to detect quercetin-induced apoptosis in RAFLSs. The cleavages of caspase-3 and caspase-9 and the accumulation of cytosolic cytochrome C were measured by western blot in quercetin-treated RAFLSs. Mitochondrial membrane potential was tested by flow cytometry. Small interfering RNAs were used to knock down the expression of protein 53 (p53) and analyze the role of p53 in quercetin-induced apoptosis in RAFLSs. DNA fragmentation assay showed that quercetin dose-dependently elevated the apoptosis of RAFLSs, accompanying with enhanced caspase-3 and caspase-9 cleavages. Moreover, quercetin caused a concentration-dependent loss of mitochondrial membrane potential and cytochrome c release to cytosol and also decreased Bcl-2/Bax ratio, indicating that quercetin-induced apoptosis is through mitochondrial pathway. Quercetin also elevated p53 phosphorylation at ser15. Pretreatment with pifithrin-α, a p53 inhibitor, significantly diminished p53 phosphorylation at the concentration of 30 μM and abrogated quercetin-induced apoptosis in a dose-dependent manner. Quercetin-induced apoptosis was also significantly blocked by p53 silencing, further suggesting the involvement of p53 in quercetin-induced apoptosis in RAFLSs. Our study indicated that quercetin-induced apoptosis of RAFLSs is through mitochondrial pathway, in which p53 plays an important role.

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Authors and Affiliations

  1. Department of Orthopaedics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jianshe Road, Zhengzhou, 450052, China

    Peng Xiao, Yingjie Hao, Xu Zhu & Xuejian Wu

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  1. Peng Xiao
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  2. Yingjie Hao
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  3. Xu Zhu
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  4. Xuejian Wu
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Correspondence to Xuejian Wu.

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Xiao, P., Hao, Y., Zhu, X. et al. p53 Contributes to Quercetin-Induced Apoptosis in Human Rheumatoid Arthritis Fibroblast-like Synoviocytes. Inflammation 36, 272–278 (2013). https://doi.org/10.1007/s10753-012-9543-5

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  • DOI: https://doi.org/10.1007/s10753-012-9543-5

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