title: Suberoylanilide Hydroxamic Acid, an Inhibitor of Histone Deacetylase, Induces Apoptosis in Rheumatoid Arthritis Fibroblast-Like Synoviocytes.
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.
authors.affiliation: Department of Nephrology, Wenzhou Central Hospital, Wenzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Cadre Health Care, Wenzhou Central Hospital, Wenzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.affiliation: Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, China.
authors.forename: Jin-Dan
authors.initials: JD
authors.lastname: Wang
authors.affiliation: Wenzhou Medical University, Wenzhou, China.
authors.forename: Qiu-Mei
authors.initials: QM
authors.lastname: Liao
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. xr_xia@163.com.
authors.forename: Xiao-Ru
authors.initials: XR
authors.lastname: Xia
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D000077337:Vorinostat; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494811:BCL2L1 protein, human; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; C498143:RELA protein, human; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D051020:bcl-X Protein; D000072000:NF-KappaB Inhibitor alpha; D000077337:Vorinostat; D053148:Caspase 3; D000111:Acetylcysteine
keywords: Bcl-2 family; apoptosis; fibroblast-like synoviocytes; nuclear factor kappa B; reactive oxygen species