title: Trichostatin A modulates intracellular reactive oxygen species through SOD2 and FOXO1 in human bone marrow-mesenchymal stem cells.
abstract: Engraft cells are often exposed to oxidative stress and inflammation; therefore, any factor that can provide the stem cells resistance to these stresses may yield better efficacy in stem cell therapy. Studies indicate that histone deacetylase (HDACs) inhibitors alleviate damage induced by oxidative stress. In this study, we investigated whether regulation of reactive oxygen species (ROS) occurs through the HDAC inhibitor trichostatin A (TSA) in human bone marrow-mesenchymal stem cells (hBM-MSCs). Intracellular ROS levels increased following exposure to hydrogen peroxide (H2 O2 ), and were suppressed by TSA treatment. Levels of the antioxidant enzyme superoxide dismutase 2 (SOD2) increased following treatment with 200 nM TSA and to a lesser level at 1-5 μM TSA. Cell protective effects against oxidative stress were significantly increased in TSA-MSCs after treatment with low doses of TSA (50-500 nM) and decreased with high doses of TSA (5-10 μM). Consistent results were obtained with immunoblot analysis for caspase3. Investigation of Forkhead box O1 (FOXO1), superoxide dismutase 2 (SOD2), and p53 levels to determine intracellular signaling by TSA in oxidative stress-induced MSCs demonstrated that expression of phosphorylated-FOXO1 and phosphorylated-SOD2 decreased in H2 O2 -treated MSCs while levels of p53 increased. These effects were reversed by the treatment of 200 nM TSA. These results suggest that the main function of ROS modulation by TSA is activated through SOD2 and FOXO1. Thus, optimal treatment with TSA may protect hBM-MSCs against oxidative stress.
authors.affiliation: Department of Biology, College of Natural Science, Chosun University, Gwangju, Korea; Department of Life Science, BK21-Plus Research Team for Bioactive Control Technology, Chosun University, Gwangju, Korea.
authors.forename: Sin-Gu
authors.initials: SG
authors.lastname: Jeong
authors.forename: Goang-Won
authors.initials: GW
authors.lastname: Cho
mesh_terms: D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D053148:Caspase 3; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D056572:Histone Deacetylase Inhibitors; D006861:Hydrogen Peroxide; D006877:Hydroxamic Acids; D016877:Oxidants; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D016159:Tumor Suppressor Protein p53; D000099156:Superoxide Dismutase 2; C085126:FOXO1 protein, human; C012589:trichostatin A
keywords: Histone deacetylase (HDAC); Mesenchymal stem cells (MSCs); Reactive oxygen species (ROS); Trichostatin A (TSA); oxidative stress