Tetrahydroxystilbene glucoside protects against LPS-induced endothelial dysfunction via inhibiting RhoA/ROCK signaling and F-actin remodeling

Gen Physiol Biophys. 2020 Sep;39(5):407-417. doi: 10.4149/gpb_2020028.

Abstract

We analyzed the role of the RhoA/ROCK pathway in regulating endothelial dysfunction triggered by LPS and the protective effects of TSG (2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucoside). Human umbilical vein endothelial cells (HUVECs) were treated with LPS at different concentrations or at different time points. Cells were also pretreated with 30 μM ROCK inhibitor Y27632 for 30 min or different concentrations of TSG for 24 h and then were incubated with 100 μg/ml LPS for another 24 h. The results showed that LPS treatment significantly reduced endothelial cell viability, increased LDH release, and promoted cell necrosis in a dose- and time-dependent manner, which was dramatically inhibited by TSG pretreatment. Furthermore, LPS induction significantly enhanced the expression of RhoA, ROCK1, and ROCK2 and the activation of ROCK; these effects were reduced by TSG pretreatment. The suppression of either RhoA or ROCK significantly improved LPS-induced endothelial cell viability, and reduced cell necrosis and LDH release. In addition, LPS treatment promoted F-actin skeleton rearrangement and contraction ring formation around the plasma membrane, which was greatly inhibited by the suppression of the RhoA/ROCK pathway or TSG pretreatment. In conclusion, TSG may inhibit F-actin cytoskeletal remodeling by blocking RhoA/ROCK signaling and thus reduce LPS-induced endothelial cell toxicity.

MeSH terms

  • Actins / metabolism*
  • Cells, Cultured
  • Glucosides / pharmacology*
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Humans
  • Lipopolysaccharides
  • Signal Transduction / drug effects*
  • Stilbenes / pharmacology*
  • rho-Associated Kinases / metabolism*
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • 2',3',4',5'-tetrahydroxystilbene-2-O-beta-D-glucoside
  • Actins
  • Glucosides
  • Lipopolysaccharides
  • Stilbenes
  • RHOA protein, human
  • ROCK1 protein, human
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein