CREB activation mediates VEGF-A's protection of neurons and cerebral vascular endothelial cells

Hsueh Te Lee, Ying Chao Chang, Yi Fang Tu, Chao Ching Huang

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Hypoxic ischemia (HI) in neonates causes significant neurodevelopmental sequelae. Pharmacological agents designed to target specific transcription factors expressed in neurons and vasculature may provide powerful therapy against HI. Vascular endothelial growth factor-A (VEGF-A) and cAMP response element-binding protein (CREB) both underlie learning and memory, and survival of the nervous system. We examined whether CREB activation is a shared pathway underlying VEGF-A's protection in neurons and cerebral vascular endothelial cells. VEGF-A was used in a HI model of rat pups and in oxygen-glucose- deprivation (OGD) models of immortalized H19-7 neurons and b.End3 cerebral vascular endothelial cells. We found that VEGF-A activated VEGF receptor-2 (VEGFR-2), phosphorylated CREB in neurons and endothelial cells, and protected against HI, and inhibiting VEGFR-2 before VEGF-A reduced the protective effect of VEGF-A in rat pups. VEGF-A also up-regulated VEGFR-2 and phosphorylated CREB, and protected H19-7 neurons and b.End3 endothelial cells against OGD. Inhibiting VEGFR-2 and extracellular signal-regulated kinase (ERK), respectively, reduced VEGF-A-induced CREB phosphorylation and protection of H19-7 and b.End3 cells against OGD. Transfecting H19-7 and b.End3 cells with a serine-133 phosphorylation mutant CREB also inhibited VEGF-A's protection of both types of cells. We conclude that CREB phosphorylation through VEGFR-2/ERK signaling is the shared pathway that underlies VEGF-A's protection of neurons and vascular endothelial cells.

Original languageEnglish
Pages (from-to)79-91
Number of pages13
JournalJournal of Neurochemistry
Volume113
Issue number1
DOIs
Publication statusPublished - Apr 2010
Externally publishedYes

Keywords

  • cAMP response element-binding protein
  • Endothelial cell
  • Hypoxia
  • Neuron
  • Vascular endothelial growth factor receptor-2
  • Vascular endothelial growth factor-A

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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