Document Detail


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.
MedLine Citation:
PMID:  16467781     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Manoranjan Santra; Mark Katakowski; Rui Lan Zhang; Zheng Gang Zhang; He Meng; Feng Jiang; Michael Chopp
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-02-08
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  26     ISSN:  0271-678X     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-21     Completed Date:  2006-10-11     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1311-22     Citation Subset:  IM    
Affiliation:
Neurology Research, Department of Neurology, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / antagonists & inhibitors,  metabolism
Aging / physiology*
Animals
Cell Line
Cell Survival / drug effects
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Extracellular Matrix Proteins / genetics,  metabolism*
Farnesyltranstransferase / antagonists & inhibitors,  metabolism
Glioma / metabolism*,  pathology*
Glucose / deficiency*,  pharmacology
Humans
Mice
Models, Biological
Oxygen / metabolism*,  pharmacology
Phosphorylation
Proteoglycans / genetics,  metabolism*
Proto-Oncogene Proteins c-akt / metabolism
Receptor, Epidermal Growth Factor / antagonists & inhibitors,  metabolism
Stem Cells / cytology,  drug effects,  metabolism*
Up-Regulation / drug effects
ras Proteins / metabolism
Grant Support
ID/Acronym/Agency:
NS23393/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p21; 0/Extracellular Matrix Proteins; 0/Proteoglycans; 0/decorin; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 50-99-7/Glucose; 7782-44-7/Oxygen; EC 2.5.1.29/Farnesyltranstransferase; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.6.5.2/ras Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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