Trichostatin a modulates intracellular reactive oxygen species through SOD2 and FOXO1 in human bone marrow-mesenchymal stem cells
Trichostatin a modulates intracellular reactive oxygen species through SOD2 and FOXO1 in human bone marrow-mesenchymal stem cells
复制标题
DOI：
10.1002/cbf.3084
复制
发表时间：
2015-01-01
影响因子：
3.6
通讯作者：
Cho, Goang-Won
中科院分区：
文献类型：
--
作者：
Jeong, Sin-Gu;Cho, Goang-Won
移植细胞经常暴露于氧化应激和炎症；因此，任何能够使干细胞抵抗这些应激的因素都可能在干细胞治疗中产生更好的疗效。研究表明组蛋白脱乙酰酶 (HDAC) 抑制剂可减轻氧化应激引起的损伤。在这项研究中，我们研究了人骨髓间充质干细胞 (hBM-MSC) 中活性氧 (ROS) 的调节是否通过 HDAC 抑制剂曲古抑菌素 A (TSA) 发生。暴露于过氧化氢 (H2O2) 后细胞内 ROS 水平增加，并被 TSA 处理抑制。用 200nM TSA 处理后，抗氧化酶超氧化物歧化酶 2 (SOD2) 的水平增加，而在 1-5M TSA 处理后，抗氧化酶超氧化物歧化酶 2 (SOD2) 的水平降低。在低剂量 TSA (50-500nM) 处理后，TSA-MSC 的细胞对抗氧化应激的保护作用显着增强，而在高剂量 TSA (5-10M) 处理后，细胞抗氧化应激的保护作用减弱。 Caspase3 的免疫印迹分析获得了一致的结果。对 Forkhead box O1 (FOXO1)、超氧化物歧化酶 2 (SOD2) 和 p53 水平进行研究，以确定氧化应激诱导的 MSC 中 TSA 的细胞内信号传导，结果表明，在 H2O2 处理的 MSC 中，磷酸化 -FOXO1 和磷酸化 -SOD2 的表达降低，而 p53 水平增加。 200nM TSA 处理可逆转这些影响。这些结果表明，TSA 调节 ROS 的主要功能是通过 SOD2 和 FOXO1 激活的。因此，TSA 的最佳治疗可以保护 hBM-MSC 免受氧化应激。版权所有 (c) 2014 约翰·威利父子有限公司
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 (H2O2), and were suppressed by TSA treatment. Levels of the antioxidant enzyme superoxide dismutase 2 (SOD2) increased following treatment with 200nM TSA and to a lesser level at 1-5M TSA. Cell protective effects against oxidative stress were significantly increased in TSA-MSCs after treatment with low doses of TSA (50-500nM) and decreased with high doses of TSA (5-10M). 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 H2O2-treated MSCs while levels of p53 increased. These effects were reversed by the treatment of 200nM 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. Copyright (c) 2014 John Wiley & Sons, Ltd.