Resveratrol induces SIRT1-Dependent autophagy to prevent H2O2-Induced oxidative stress and apoptosis in HTR8/SVneo cells

• Published in: Placenta (Eastbourne) 2020-02, Vol.91, p.11-18
• Main Authors: Wang, Ping, Huang, Chen-xi, Gao, Jun-jun, Shi, Ying, Li, Hong, Yan, Huan, Yan, Shu-jun, Zhang, Zhan
• Format: Article
• Language: English
• Subjects: Apoptosis; Autophagy; Oxidative stress; Pre-eclampsia; Resveratrol; SIRT1
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2020.01.002

Pre-eclampsia (PE) is a serious complication of pregnancy, and the likely pathogenic basis of early onset PE are placental dysfunction and increased oxidative stress. Resveratrol (RES) is a potent antioxidant which has shown beneficial effects in many diseases. The aim of this study was to investigate the protective effects of RES against oxidative stress-induced damage in trophoblasts, and elucidate the potential mechanisms. We established an in vitro model of oxidative stress by exposing the human first-trimester extravillous trophoblast cell line HTR8/SVneo to H2O2. The level of oxidative stress was reflected by ROS, MDA and SOD. The viability of cells was determined by the MTS assay. Apoptosis was detected using Annexin V-FITC staining and flow cytometry. Levels of SIRT1(sirtuin 1) and autophagy-related proteins (LC3, Beclin-1, p62) were detected by western blot. Autophagosomes were observed by transmission electron microscopy (TEM). Pre-treatment with RES significantly ameliorated H2O2-induced cytotoxicity, morphological damage, oxidative stress and apoptosis. Mechanistically, RES restored the levels of SIRT1 and autophagy-related proteins including LC3-II, Beclin-1 and p62 that were dysregulated by H2O2. Blocking autophagy by 3-methyladenine (3-MA) completely abolished the protective effects of RES, as did knocking down SIRT1. RES may protect human trophoblasts against H2O2-induced oxidative stress by activating SIRT1-dependent autophagy, and therefore has therapeutic potential in PE. •Resveratrol protects HTR-8/SVneo cells from H2O2-induced oxidative stress and apoptosis.•Resveratrol induces autophagy and upregulates SIRT1 in HTR-8/SVneo cells.•SIRT1 knockdown inhibits resveratrol-induced autophagy and protective effects.•Resveratrol has therapeutic potential in preeclampsia.