Vascular endothelial growth factor protects cultured rat hippocampal neurons against hypoxic injury via an antiexcitotoxic, caspase-independent mechanism.
The authors investigated the effect of vascular endothelial growth factor (VEGF) on hypoxic injury of cultured rat hippocampal neurons. Treatment with glutamate receptor antagonists prevented hypoxic neuron death. The same magnitude of protection was observed in cultures treated with VEGF, which also reduced excitotoxic neuron death induced directly by an exposure to -methyl-d-aspartate. Vascular endothelial growth factor did not alter the activation of the transcription factor nuclear factor-kappaB during hypoxia and protected cells in a PI-3-kinase-independent manner. Vascular endothelial growth factor failed to protect against staurosporine-induced, caspase-dependent apoptosis. These data suggest that VEGF-induced protection against hypoxic injury primarily involves the inhibition of excitotoxic processes.
D000818:Animals; D001483:Base Sequence; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects*; D002478:Cells, Cultured; D017931:DNA Primers; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D006624:Hippocampus / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007700:Kinetics; D008222:Lymphokines / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors*; D020033:Protein Isoforms / Q000494:pharmacology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D029867:Xenopus Proteins
D017931:DNA Primers; D016228:Endothelial Growth Factors; D016326:Extracellular Matrix Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D020033:Protein Isoforms; D012261:Ribonucleoproteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D029867:Xenopus Proteins; C068598:Msi1 protein, Xenopus; D016202:N-Methylaspartate; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases