TY - JOUR
T1 - Vascular endothelial growth factor rescues HN33 neural cells from death induced by serum withdrawal
AU - Kun Lin Jin, Lin Jin
AU - Xiao Ou Mao, Ou Mao
AU - Greenberg, D. A.
N1 - Funding Information:
Supported by National Institutes of Health Grant NS37695.
PY - 2000
Y1 - 2000
N2 - 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 IκB-α and nuclear translocation of the transcription factor NF-κB. Withdrawal of serum for 24 h reduced HN33 cell viability by ~50% in the absence of VEGF, but by only ~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-κB. Thus, VEGF, like other neurotrophic factors, could exert protective effects in acute or chronic neurodegenerative disorders.
AB - 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 IκB-α and nuclear translocation of the transcription factor NF-κB. Withdrawal of serum for 24 h reduced HN33 cell viability by ~50% in the absence of VEGF, but by only ~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-κB. Thus, VEGF, like other neurotrophic factors, could exert protective effects in acute or chronic neurodegenerative disorders.
KW - Akt
KW - Growth factors
KW - HN33 cells
KW - Phosphatidylinositol 3'-kinase
KW - VEGF
KW - VEGFR-2 receptor
UR - http://www.scopus.com/inward/record.url?scp=0033848792&partnerID=8YFLogxK
U2 - 10.1385/jmn:14:3:197
DO - 10.1385/jmn:14:3:197
M3 - Article
C2 - 10984196
AN - SCOPUS:0033848792
SN - 0895-8696
VL - 14
SP - 197
EP - 203
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
IS - 3
ER -