MiR-34a/sirtuin-1/foxo3a is involved in genistein protecting against ox-LDL-induced oxidative damage in HUVECs

• Published in: Toxicology letters 2017-08, Vol.277, p.115-122
• Main Authors: Zhang, Huaping, Zhao, Zhenxiang, Pang, Xuefen, Yang, Jian, Yu, Haixia, Zhang, Yinhong, Zhou, Hui, Zhao, Jiahui
• Format: Article
• Language: English
• Subjects: Acetylation; Active Transport, Cell Nucleus; Antioxidants - pharmacology; Atherosclerosis; Catalase - metabolism; Cells, Cultured; Cytoprotection; Dose-Response Relationship, Drug; Forkhead Box Protein O3 - genetics; Forkhead Box Protein O3 - metabolism; foxo3a; Genistein; Genistein - pharmacology; Glutathione - metabolism; Glutathione Peroxidase - metabolism; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - enzymology; Human Umbilical Vein Endothelial Cells - pathology; Humans; Lipoproteins, LDL - toxicity; MicroRNAs - genetics; MicroRNAs - metabolism; miR-34a; Oxidative damage; Oxidative Stress - drug effects; RNA Interference; Signal Transduction - drug effects; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Sirtuin-1; Superoxide Dismutase - metabolism; Transfection
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2017.07.216

•The antioxidation of genistein was correlated with the upregulation of sirtuin-1 via inhibiting miR-34a.•The antioxidation of genistein was associated with miR-34a/sirtuin-1-mediated nuclear translocation and deacetylation of foxo3a, accompanying with the enhanced expressions of MnSOD and CAT.•MiR-34a/sirtuin-1/foxo3a might play an important role in genistein reversing ox-LDL-induced oxidative damage in HUVECs. The antioxidant activity of genistein is associated with preventing atherosclerosis; however, the underlying mechanisms are not fully understood. In this study, human umbilical vein endothelial cells (HUVECs) were pretreated with genistein at different concentrations (10nM, 100nM and 1000nM) for 6h and then exposed to ox-LDL (50mg/L) for another 24h. Results showed that genistein restrained reactive oxygen species (ROS) and malondialdehyde (MDA) production, and ameliorated the inhibitory effect on superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) activity elicited by ox-LDL stimulation. The effects of genistein were correlated with the upregulation of sirtuin-1 via inhibiting miR-34a, and were abolished by sirtuin-1 siRNA or miR-34a mimic. Moreover, the antioxidation of genistein was associated with miR-34a/sirtuin-1-mediated nuclear translocation and deacetylation of foxo3a, accompanying with the enhanced expressions of MnSOD and CAT. The present study suggests that miR-34a/sirtuin-1/foxo3a might play an important role in genistein reversing ox-LDL-induced oxidative damage in HUVECs.