title: Induction of vascular endothelial growth factor receptors and phosphatidylinositol 3'-kinase/Akt signaling by global cerebral ischemia in the rat.
abstract: Vascular endothelial growth factor is an angiogenic peptide that binds to tyrosine kinase receptors on target cells to activate signal transduction pathways involving phosphatidylinositol 3'-kinase and the serine-threonine protein kinase, Akt. To determine whether this signaling pathway is activated in cerebral ischemia, we examined the expression of vascular endothelial growth factor receptors 1 and 2, and phosphatidylinositol 3'-kinase-activated phospho-Akt, in the cerebral cortex and hippocampus following transient global cerebral ischemia in the rat. Western blot analysis and immunocytochemistry demonstrated induction of vascular endothelial growth factor receptor 1 and 2 expression, and of anti-phosphatidylinositol 3'-kinase-immunoprecipitated phospho-Akt, in vulnerable regions of the cortex and hippocampus after 15 min of global ischemia and 4-72 h of reperfusion. These findings demonstrate that vascular endothelial growth factor receptors and receptor-coupled signal transduction pathways are induced in ischemic brain in vivo, and could therefore participate in endogenous neuroprotective responses to ischemia.
authors.affiliation: Buck Center for Research in Aging, PO Box 638, CA 94948-0638, Novato, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Jin
authors.forename: X O
authors.initials: XO
authors.lastname: Mao
authors.forename: T
authors.initials: T
authors.lastname: Nagayama
authors.forename: P C
authors.initials: PC
authors.lastname: Goldsmith
authors.forename: D A
authors.initials: DA
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D017978:Receptors, Growth Factor / Q000096:biosynthesis*; D040262:Receptors, Vascular Endothelial Growth Factor; D015398:Signal Transduction
chemical_list: 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; C494920:Akt1 protein, rat