Protection of adult mouse progenitor cells and human glioma cells by de novo decorin expression in an oxygen- and glucose-deprived cell culture model system

J Cereb Blood Flow Metab. 2006 Oct;26(10):1311-22. doi: 10.1038/sj.jcbfm.9600285. Epub 2006 Feb 8.

Abstract

We employed an in vitro hypoxia cell culture model system and gene transfer technology to examine the effect of the decorin gene on cell survival against oxygen and glucose deprivation (OGD). Ectopic expression of decorin in subventricular zone (SVZ) cells from adult male mouse brain and human glioblastoma U-87 cells kept the cells viable against 24 h of OGD. Fewer than 1% of decorin-synthesizing cells were apoptotic after 12 h of OGD. In contrast, 100% of the control cells were apoptotic even after 4 h of OGD. De novo decorin synthesis in SVZ and U-87 cells induced expression of p21, p27 and Ras, AKT (acutely transforming retrovirus AKT8 in rodent T-cell lymphoma), and phosphorylated AKT. Blocking of phosphoinositide 3-kinase (PI-3K), Ras, and the epidermal growth factor receptor with specific inhibitors had no effect on induction of Ras, p21, and p27 at the messenger RNA level in decorin-synthesizing SVZ and U-87 cells. PI-3K inhibitors significantly increased apoptosis in decorin-expressing cells. Our data indicate that induction of p21, p27, Ras, AKT, and phosphorylated AKT by decorin inhibits apoptosis and protects U-87 and SVZ cells against OGD. Therefore, our data suggest that decorin is a potent trophic factor that protects neuronal progenitor cells and glioma cells from OGD.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / physiology*
  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Decorin
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Farnesyltranstransferase / antagonists & inhibitors
  • Farnesyltranstransferase / metabolism
  • Glioma / metabolism*
  • Glioma / pathology*
  • Glucose / deficiency*
  • Glucose / pharmacology
  • Humans
  • Mice
  • Models, Biological
  • Oxygen / metabolism*
  • Oxygen / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Proteoglycans / genetics
  • Proteoglycans / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Up-Regulation / drug effects
  • ras Proteins / metabolism

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • DCN protein, human
  • Dcn protein, mouse
  • Decorin
  • Extracellular Matrix Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Proteoglycans
  • Cyclin-Dependent Kinase Inhibitor p27
  • Farnesyltranstransferase
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt
  • ras Proteins
  • Glucose
  • Oxygen