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

Authors
  • Zhang, Huaping1
  • Zhao, Zhenxiang2
  • Pang, Xuefen3
  • Yang, Jian2
  • Yu, Haixia2
  • Zhang, Yinhong4
  • Zhou, Hui2
  • Zhao, Jiahui2
  • 1 Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China. Electronic address: [email protected] , (China)
  • 2 Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China. , (China)
  • 3 Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China. , (China)
  • 4 Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Laboratory Animal Center, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China. , (China)
Type
Published Article
Journal
Toxicology letters
Publication Date
Aug 05, 2017
Volume
277
Pages
115–122
Identifiers
DOI: 10.1016/j.toxlet.2017.07.216
PMID: 28688900
Source
Medline
Keywords
License
Unknown

Abstract

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.

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