Korean J Physiol Pharmacol.  2020 Nov;24(6):473-479. 10.4196/kjpp.2020.24.6.473.

2,3,5,4’-Tetrahydroxystilbene-2-O-β-D-Glucoside modulated human umbilical vein endothelial cells injury under oxidative stress

Affiliations
  • 1College of Basic Medicine & Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China
  • 2College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China

Abstract

Endothelial cell injury is a major contributor to cardiovascular diseases. The 2,3,5,4’-Tetrahydroxystilbene-2-O-β-D-Glucoside (TSG) contributes to alleviate human umbilical vein endothelial cells (HUVECs) injury through mechanisms still know a little. This study aims to clarify the TSG effects on gene expression (mRNA and microRNA) related to oxidative stress and endoplasmic reticulum stress induced by H2O2 in HUVECs. We found that TSG significantly reduced the death rate of cells and increased intracellular superoxide dismutase activity. At qRT-PCR, experimental data showed that TSG significantly counteracted the expressions of miR-9-5p, miR-16, miR-21, miR-29b, miR-145-5p, and miR-204-5p. Besides, TSG prevented the expression of ATF6 and CHOP increasing. In contrast, TSG promoted the expression of E2F1. In conclusion, our results point to the obvious protective effect of TSG on HUVECs injury induced by H2O2, and the mechanism may through miR16/ATF6/ E2F1 signaling pathway.

Keyword

Endoplasmic reticulum stress; Human umbilical vein endothelial cells; MicroRNAs; Oxidative damage; 2,3,5,4’-Tetrahydroxystilbene-2-O-β-D-Glucoside

Figure

  • Fig. 1 H2O2 exposure induced the decrease of cell viability. HUVECs stimulated with or without on by H2O2. Values are expressed as mean ± standard deviation (n = 3). HUVECs, human umbilical vein endothelial cells. ##p < 0.01 vs. control.

  • Fig. 2 TSG pre-treatment improved cell viability. TSG Treatment on HUVECs untreated (basal) (A) and H2O2-induced (B) for 24 h. Values are expressed as mean ± standard deviation (n = 3). TSG, 2,3,5,4’-Tetrahydroxystilbene-2-O-β-D-Glucoside; HUVECs, human umbilical vein endothelial cells. #p < 0.05 and ##p < 0.05 vs. control; *p < 0.05 and **p < 0.05 vs. H2O2 group.

  • Fig. 3 TSG pre-treatment suppressed apoptotic cell death. Representative images of staining with Annexin V-FITC (green) and PI (red) acquired using a laser scanning microscope (scale ×100 μm). The images were captured within the same field and then merged. Values are expressed as mean ± standard deviation (n = 3). TSG, 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside; PI, propidium iodide.

  • Fig. 4 TSG pre-treatment ameliorated H2O2 induced loss of SOD in HUVECs. SOD activity was been detected. Values are expressed as mean ± standard deviation (n = 3). TSG, 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside; SOD, superoxide dismutase; HUVECs, human umbilical vein endothelial cells. #p < 0.05 vs. control; *p < 0.05 vs. H2O2 group.

  • Fig. 5 Effect of TSG pre-treatment in miRNA expression in H2O2 induced HUVECs. qRT-PCR was used to detected the (A) miR-9-5p, (B) miR-16, (C) miR-21, (D) miR-29b, (E) miR-145-5p, and (F) miR-204-5p synthesis. Values are expressed as mean ± standard deviation (n = 3). TSG, 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside; HUVECs, human umbilical vein endothelial cells. #p < 0.05 and ##p < 0.01 vs. control; *p < 0.05 and **p < 0.01 vs. H2O2 group.

  • Fig. 6 Effect of TSG on ER stress in HUVECs. qRT-PCR was used to detect the (A) ATF4, (B) ATF6, (C) CHOP, (D) GRP78, and (E) E2F1 mRNA synthesis. Values are expressed as mean ± standard deviation (n = 3). TSG, 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside; ER, endoplasmic reticulum; HUVECs, human umbilical vein endothelial cells. #p < 0.05 and ##p < 0.01 vs. control; *p < 0.05 and **p < 0.01 vs. H2O2 group.

  • Fig. 7 The predicted result of TargetScanHuman database.


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