Vascular endothelial growth factor receptor 2 (VEGFR2, Flk-1/KDR) protects HEK293 cells against CoCl(2) -induced hypoxic toxicity

Cell Biochem Funct. 2012 Mar;30(2):151-7. doi: 10.1002/cbf.1829. Epub 2011 Nov 16.

Abstract

Vascular endothelial growth factor (VEGF) is an endothelium-specific mitogen and a promising inducer of angiogenesis and lymphangiogenesis. The VEGF receptors on endothelial cell membrane include the tyrosine kinases VEGFR-1 (Flt-1), VEGFR-2 (Flk-1/KDR) and VEGFR-3 (Flt-4). KDR is a major mediator of mitogenic, angiogenic and permeability-enhancing effects of VEGF. KDR is upregulated in response to hypoxia, a major inducer of VEGF gene transcription. A HEK293 cell line overexpressing KDR was established under cell hypoxic stress to explore the function of KDR. A hypoxia-inducing agent, cobalt chloride (CoCl(2)) was applied to detect whether KDR was able to prevent against chemical hypoxic toxicity. The results indicate that KDR attenuated CoCl(2)-induced cell injury in HEK293 cells. Furthermore, the underlying mechanisms may be explained by the increased expression of Bcl-2, AKT1 and phosphorylated AKT, key members of cell survival pathway, and decreased expression of pro-apoptosis protein Bax.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cobalt / toxicity*
  • HEK293 Cells
  • Humans
  • Hypoxia / chemically induced
  • Hypoxia / genetics
  • Hypoxia / metabolism*
  • Hypoxia / physiopathology
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Cobalt
  • Vascular Endothelial Growth Factor Receptor-2
  • Proto-Oncogene Proteins c-akt
  • cobaltous chloride