Vascular endothelial growth factor rescues HN33 neural cells from death induced by serum withdrawal.
Vascular endothelial growth factor (VEGF) is an angiogenic factor with neurotrophic effects in the peripheral nervous system. To determine if VEGF can also promote the survival of central neurons, we examined its effect on HN33 (mouse hippocampal neuron x neuroblastoma) cells deprived of serum. Serum-deprived HN33 cells expressed VEGFR-2 receptors, which, in the presence of VEGF, interacted with the downstream signaling molecules phosphatidylinositol 3'-kinase and phospho-Akt, as demonstrated by immunoprecipitation and Western blotting. Treatment of serum-deprived HN33 cells with VEGF also stimulated the phosphorylation of IkappaB-alpha and nuclear translocation of the transcription factor NF-kappaB. Withdrawal of serum for 24 h reduced HN33 cell viability by approximately 50% in the absence of VEGF, but by only approximately 20% in the presence of 100 ng/mL of VEGF. These findings support a neurotrophic role for VEGF in the central nervous system, which may be mediated through VEGFR-2 receptors, the protein kinases phosphatidylinositol 3'-kinase and Akt, and the transcription factor NK-kappaB. Thus, VEGF, like other neurotrophic factors, could exert protective effects in acute or chronic neurodegenerative disorders.
Jin
K L
KL
Buck Center for Research in Aging, Novato, CA, USA.
Mao
X O
XO
Greenberg
D A
DA
D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology*; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology; D006822:Hybrid Cells; D020672:I-kappa B Proteins / Q000032:analysis; D008222:Lymphokines / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000032:analysis; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000032:analysis / Q000378:metabolism; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000032:analysis / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013347:Subcellular Fractions / Q000737:chemistry / Q000201:enzymology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D001798:Blood Proteins; D016228:Endothelial Growth Factors; D020672:I-kappa B Proteins; D008222:Lymphokines; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D020794:Receptor Protein-Tyrosine Kinases; D017978:Receptors, Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors