VEGFR-2-mediated increased proliferation and survival in response to oxygen and glucose deprivation in PlGF knockout astrocytes: J.Neurochem.

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TypeArticle
Journal titleJournal Of Neurochemistry
Volume107
Issue3
Pages756767; # of pages: 12
Subjectanalysis; Animals; Astrocytes; Blotting,Western; Brain Ischemia; Canada; cell; Cell Hypoxia; Cell Proliferation; Cell Survival; Cells,Cultured; deficiency; Enzyme-Linked Immunosorbent Assay; EXPRESSION; Gene Expression; Gene Expression Profiling; genetics; Glucose; Immunohistochemistry; Lasers; membrane; metabolism; Mice; Mice,Knockout; Microdissection; Microscopy; Microscopy,Confocal; NUCLEAR; Oxygen; pathology; PATHWAY; Phenotype; physiology; Pregnancy; Pregnancy Proteins; protein; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Rna; RNA,Messenger; Role; Signal Transduction; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2
AbstractIn hypoxic/ischemic conditions, astrocytes are involved in neuroprotection and angiogenesis. Vascular endothelial growth factor (VEGF) induces angiogenesis and exhibits neuroprotective and neurotrophic properties. However, the role of placental growth factor (PlGF), a VEGF homolog, in these processes is unclear. Therefore, proliferation and survival studies were performed on PlGF knockout (PlGF-/-) and wild-type (PlGF+/+) mouse astrocytes. A significant increase in cell proliferation and survival to oxygen and glucose deprivation (OGD) was observed in PlGF-/- compared to PlGF+/+ astrocytes. Interestingly, no PlGF protein expression was detected in PlGF+/+ astrocytes and no changes in VEGF protein levels were observed between the two genotypes. Real-time PCR and immunocytochemistry showed over-expression of VEGF receptor-2 (VEGFR-2) in PlGF-/- compared with PlGF+/+ astrocytes. Confocal microscopy revealed nuclear, membrane, and cytoplasmic localization of VEGFR-2. In vivo over-expression of VEGFR-2 mRNA was also detected in PlGF-/- compared with PlGF+/+ astrocytes. Stimulation with VEGF165 resulted in increased proliferation in PlGF-/- compared with PlGF+/+ astrocytes. This effect was blocked by the VEGFR-2 antagonist, VEGF165b. The enhanced proliferation of PlGF-/- astrocytes correlated with increased phospho-extracellular-signal-regulated kinase-1/2 levels, while the resistance to OGD was independent of the phosphatidylinositol 3'-kinase/Akt pathway. These results suggest that VEGFR-2 mediates the enhanced proliferative/OGD resistant phenotype observed in PlGF-/- astrocytes
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedNo
NRC numberFREITASANDRADE2008
NPARC number9371685
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Record identifier00c6ec89-aede-40cf-a732-3243acba2cb7
Record created2009-07-10
Record modified2016-05-09
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