Zuo Mengna, Tong Ruiying, He Xiaoying, Liu Yang, Liu Jiwei, Liu Shujun, Liu Ying, Cao Junwei, Ma Libing
School of Life Science and Technology, Inner Mongolia University of Science and Technology, Baotou, China.
College of Life Science, Inner Mongolia Agricultural University, Hohhot, China.
Free Radic Res. 2023 Jan;57(1):47-60. doi: 10.1080/10715762.2023.2190862. Epub 2023 Mar 22.
High concentrations of antioxidants can exert pro-oxidative effects, elevate the level of intracellular reactive oxygen species (ROS), and cause oxidative stress in cells. We previously found that high concentrations of curcumin, a natural polyphenol antioxidant, elevated ROS levels and upregulated the expression of histone deacetylase 1 (HDAC1) in human gastric cancer cells (hGCCs); however, its potential mechanisms and subsequent functions have not been elucidated. In the present study, we treated hGCCs with high concentrations of curcumin, detected several indicators of oxidative stress, and investigated the mechanism of curcumin-treatment-mediated HDAC1 upregulation and its effect on histone acetylation. The results showed that curcumin treatment caused oxidative stress in hGCCs and upregulated HDAC1/2 expression the forkhead box O (FOXO) signaling pathway, ultimately leading to the deacetylation of histones in hGCCs. Moreover, HDAC1/2 mediates the deacetylation of FOXOs and promotes their transcription activities, implying a positive feedback loop between FOXOs and HDAC1/2. These findings present a mechanism by which oxidative stress induces histone deacetylation in hGCCs.
高浓度的抗氧化剂可发挥促氧化作用，提高细胞内活性氧（ROS）水平，并在细胞中引起氧化应激。我们之前发现，高浓度的姜黄素（一种天然多酚抗氧化剂）可提高人胃癌细胞（hGCCs）中的ROS水平并上调组蛋白去乙酰化酶1（HDAC1）的表达；然而，其潜在机制及后续功能尚未阐明。在本研究中，我们用高浓度姜黄素处理hGCCs，检测了氧化应激的几个指标，并研究了姜黄素处理介导的HDAC1上调机制及其对组蛋白乙酰化的影响。结果表明，姜黄素处理在hGCCs中引起氧化应激并上调HDAC1/2表达，通过叉头框O（FOXO）信号通路，最终导致hGCCs中组蛋白的去乙酰化。此外，HDAC1/2介导FOXOs的去乙酰化并促进其转录活性，这意味着FOXOs与HDAC1/2之间存在正反馈回路。这些发现揭示了氧化应激在hGCCs中诱导组蛋白去乙酰化的一种机制。
