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Suberoylanilide Hydroxamic Acid, an Inhibitor of Histone Deacetylase, Induces Apoptosis in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

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Abstract

Here, we explored the effects of suberoylanilide hydroxamic acid (SAHA) on the viability and apoptosis of rheumatoid arthritis of fibroblast-like synoviocytes (rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS)). FLS obtained from RA patients were treated with SAHA. SAHA significantly inhibited the viability of RA FLS in a concentration-dependent manner up to 5 μM. SAHA-treated FLS showed a significant increase in the percentage of apoptosis and the expression and activity of caspase-3 and higher intracellular ROS levels. N-acetyl-l-cysteine (NAC) pretreatment significantly attenuated SAHA-induced apoptosis, decreasing the percentage of apoptosis by about 60 %. A significant decline in phosphorylated IκBα and nuclear factor kappa B (NF-κB) p65 and concomitant increase in total IκBα were shown in SAHA-treated FLS. Additionally, the levels of anti-apoptotic Bcl-2 proteins (Bcl-xL and Mcl-1) were significantly reduced by SAHA. Collectively, SAHA induces apoptosis of RA FLS, at least partially, through generation of ROS and suppression of NF-κB activation and Bcl-xL and Mcl-1 expression.

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Author information

Authors and Affiliations

  1. Department of Nephrology, Wenzhou Central Hospital, Wenzhou, China

    Hui Chen

  2. Department of Cadre Health Care, Wenzhou Central Hospital, Wenzhou, China

    Jing Pan

  3. Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, China

    Jin-dan Wang

  4. Wenzhou Medical University, Wenzhou, China

    Qiu-mei Liao

  5. Department of Rheumatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Xiao-ru Xia

Authors
  1. Hui Chen
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  2. Jing Pan
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  3. Jin-dan Wang
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  4. Qiu-mei Liao
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  5. Xiao-ru Xia
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Correspondence to Xiao-ru Xia.

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Chen, H., Pan, J., Wang, Jd. et al. Suberoylanilide Hydroxamic Acid, an Inhibitor of Histone Deacetylase, Induces Apoptosis in Rheumatoid Arthritis Fibroblast-Like Synoviocytes. Inflammation 39, 39–46 (2016). https://doi.org/10.1007/s10753-015-0220-3

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  • DOI: https://doi.org/10.1007/s10753-015-0220-3

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