Activation of Wnt3α/β-catenin signal pathway attenuates apoptosis of the cerebral microvascular endothelial cells induced by oxygen-glucose deprivation

Biochem Biophys Res Commun. 2017 Aug 19;490(2):71-77. doi: 10.1016/j.bbrc.2017.03.130. Epub 2017 Mar 25.

Abstract

Brain microvascular endothelial cells (BMECs) play vital roles in cerebral ischemia, during which many signal pathways mediate BMECs apoptosis. In this study, we explored the potential role of Wnt3α/β-catenin signal in BMECs apoptosis induced by ischemia. Here, we found that oxygen-glucose deprivation (OGD) could induce apoptosis of BMECs with Wnt3a mRNA expression decrease. Meanwhile, activation Wnt3a/β-catenin signal with exogenous Wnt3α protein (100 ng/ml) or Lithium Chloride (LiCl, 4 mM) decreased significantly apoptosis of BMECs induced by OGD with increasing expression of Bcl-2 in the whole cell and β-catenin in the nucleus. But, inhibition Wnt3a/β-catenin signal with DKK1 (100 ng/ml) or 2.4-diamino quinazoline (DQ, 0.2 μM) increased apoptosis of BMECs with decreasing expression of Bcl-2. These results suggest that activation Wnt3α/β-catenin signal attenuate apoptosis of BMECs induced by ischemia.

Keywords: Apoptosis; Brain microvascular endothelial cells (BMECs); Oxygen-glucose deprivation (OGD); Wnt3α/β-catenin signal.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cerebrovascular Circulation / drug effects
  • Cerebrum / blood supply*
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Glucose / deficiency*
  • Glucose / metabolism
  • Hypoxia / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lithium Chloride / pharmacology
  • Microvessels / cytology
  • Oxygen / metabolism*
  • Quinazolines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Wnt Signaling Pathway / drug effects
  • Wnt3 Protein / agonists
  • Wnt3 Protein / metabolism*
  • beta Catenin / agonists
  • beta Catenin / metabolism*

Substances

  • Ctnnb1 protein, rat
  • Dkk1 protein, rat
  • Intercellular Signaling Peptides and Proteins
  • Quinazolines
  • Wnt3 Protein
  • Wnt3 protein, rat
  • beta Catenin
  • 2,4-diaminoquinazoline
  • Lithium Chloride
  • Glucose
  • Oxygen