KEAP1型
氧化应激
化学
细胞凋亡
活性氧
细胞生物学
丙二醛
信号转导
白藜芦醇
生物化学
生物
转录因子
基因
作者
Ye Zhang,Gaoyuan Wang,Taorong Wang,Wei Cao,Lixia Zhang,Xiaoyu Chen
摘要
Abstract Resveratrol (Res) is a polyphenolic compound that has a variety of biological functions and activities. This study aimed to explore the mechanisms of the antioxidant and proapoptotic effects of Res in H 2 O 2 ‐treated rheumatoid arthritis fibroblast‐like synoviocytes (RA‐FLSs) by the Nrf2–Keap1 signaling pathway. We found that 5 µM H 2 O 2 promoted cell proliferation and increased intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) content in RA‐FLSs. However, Res could reverse these effects in 5 µMH2O2‐treated RA‐FLSs by (1) promoting expression of nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1), (2) reducing expression of Kelch‐like ECH–related protein 1 (Keap1), (3) inhibiting production of ROS and MDA, (4) blocking activation of nuclear factor‐κB (NF‐κB) p65, (5) inhibiting cell proliferation and migration, and (6) activating Bcl‐2/Bax to induce apoptosis. After lentiviral silencing of Nrf2 (siNrf2) mRNA expression in RA‐FLSs, Res addition did not increase the expression of Nrf2 or HO‐1 to reduce the production of mitochondrial ROS caused by 5 µM H 2 O 2 . Res reduced the Bcl‐2/Bax ratio, but siNrf2 reduced the ability of Res to promote apoptosis. We conclude that Res inhibits ROS production by activating the Nrf2 pathway, thereby inhibiting activation of NF‐κB and proliferation and migration of RA‐FLSs, to induce apoptosis. Targeting the Nrf2–Keap1 pathway may be a relevant aim of using Res in the treatment of RA.
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