Vascular endothelial growth factor (VEGF) signaling regulates hippocampal neurons by elevation of intracellular calcium and activation of calcium/calmodulin protein kinase II and mammalian target of rapamycin.

Authors: Kim, BW  Choi, M  Kim, YS  Park, H  Lee, HR  Yun, CO  Kim, EJ  Choi, JS  Kim, S  Rhim, H  Kaang, BK  Son, H 
Citation: Kim BW, etal., Cell Signal. 2008 Apr;20(4):714-25. Epub 2007 Dec 17.
Pubmed: (View Article at PubMed) PMID:18221855
DOI: Full-text: DOI:10.1016/j.cellsig.2007.12.009

The present study was undertaken to characterize neuronal activity-dependent expression and release of vascular endothelial growth factor (VEGF) from rat hippocampal neurons and its contribution to neuronal functions. Increased levels of VEGF(164) mRNA were evident both in cultured neurons and slices, but not astrocytes, following membrane depolarization with KCl. Activity-dependent expression of VEGF, as well as its release, was dependent on the activation of the N-methyl-d-aspartate receptors or L-type voltage-activated calcium channels. A brief (10 min) application of recombinant VEGF(165) to neurons elicited a slow rise in cytosolic Ca(2+) in a VEGFR2 dependent manner. The VEGF-induced Ca(2+) responses required Ca(2+) influx, phospholipase Cgamma and Ca(2+) stores. An inhibitor of transient receptor potential canonical channels reduced the VEGF-induced Ca(2+) responses by 50%, suggesting the involvement of transient receptor potential canonical channels in the VEGF-mediated responses. The same brief stimulus with VEGF led to long-term synaptic enhancement dependent on protein synthesis. VEGF had prominent effects on the activation calcium/calmodulin protein kinase II and cAMP responsive element binding protein as well as extracellular signal-regulated protein kinase and mammalian target of rapamycin-all in a VEGFR2 dependent manner. Our findings suggest that VEGF released from neuronal cells plays a local role in Ca(2+) influx and synaptic transmission that may influence the generation of long-term changes in synaptic efficacy.

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CRRD Object Information
CRRD ID: 2292019
Created: 2008-04-09
Species: All species
Last Modified: 2008-04-09
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.