| Modification of endothelial NO synthase through protein phosphorylation after forebrain cerebral ischemia/reperfusion. | |
MedLine Citation:
|
PMID: 15375304 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND AND PURPOSE: Production of NO by endothelial NO synthase (eNOS) is thought to play a neuroprotective role after cerebral ischemia. The vascular endothelial growth factor (VEGF) contributes to activation of eNOS by Ca2+/calmodulin and also stimulates the protein kinase Akt, which directly phosphorylates eNOS on Ser1177 and increases enzyme activity. Although the expression of VEGF has been studied in ischemic stroke models, the activation of eNOS after cerebral ischemia has not been investigated. The purpose of the present study was to clarify molecular mechanisms underlying the regulation of eNOS activity through protein phosphorylation in postischemic processes. METHODS: Sprague-Dawley rats were subjected to forebrain cerebral ischemia for 15 minutes with hypotension and reperfusion for up to 24 hours. Western blot analysis and ELISAs were used to study the temporal profiles of Akt, phospho-Akt at Ser437, eNOS, phospho-eNOS at Ser1177, and VEGF expression, respectively. Immunohistochemical studies were performed to examine the spatial expression patterns of phospho-Akt at Ser437 and phospho-eNOS at Ser1177. RESULTS: Increase in phospho-Akt at Ser437 was observed transiently 0.5 to 2 hours after reperfusion, whereas elevation of phospho-eNOS at Ser1177 and VEGF expression was observed from 6 hours after reperfusion. Endothelial cells in the microvessels were the major source of eNOS phosphorylated at Ser1177 at the 12-hour time point. CONCLUSIONS: Increase in Ser1177 phospho-eNOS occurs in endothelial cells of microvessels after ischemic episodes with temporal expression of VEGF, pointing to a contribution to the autoregulation of postischemic brain damage. |
Authors:
|
Koji Osuka; Yasuo Watanabe; Nobuteru Usuda; Ayami Nakazawa; Masaaki Tokuda; Jun Yoshida |
Related Documents
:
|
16868034 - Fibroblast growth factor-2 mediates angiotensin-converting enzyme inhibitor-induced ang... 16691504 - Potentiation of angiogenic switch in capillary endothelial cells by camp: a cross-talk ... 19349964 - Genipin inhibits endothelial exocytosis via nitric oxide in cultured human umbilical ve... 16631534 - Critical role of endothelial cell-derived nitric oxide synthase in sickle cell disease-... 20003814 - The influence of exon 7 phe389leu polymorphism on p120 catenin interactions with e-cadh... 15325284 - Bi-directional cell contact-dependent regulation of gene expression between endothelial... |
Publication Detail:
|
Type: Journal Article Date: 2004-09-16 |
Journal Detail:
|
Title: Stroke; a journal of cerebral circulation Volume: 35 ISSN: 1524-4628 ISO Abbreviation: Stroke Publication Date: 2004 Nov |
Date Detail:
|
Created Date: 2004-10-29 Completed Date: 2005-05-11 Revised Date: 2009-11-19 |
Medline Journal Info:
|
Nlm Unique ID: 0235266 Medline TA: Stroke Country: United States |
Other Details:
|
Languages: eng Pagination: 2582-6 Citation Subset: IM |
Affiliation:
|
Department of Neurosurgery, Nagoya University Graduate School of Medicine, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Brain / enzymology Brain Ischemia / enzymology* Homeostasis Male Nitric Oxide Synthase / metabolism* Nitric Oxide Synthase Type III Phosphorylation Protein-Tyrosine Kinases / metabolism Rats Rats, Sprague-Dawley Vascular Endothelial Growth Factor A / metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Vascular Endothelial Growth Factor A; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, rat; EC 2.7.10.1/Protein-Tyrosine Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Glutamate receptor blockade attenuates glucose hypermetabolism in perihematomal brain after experime...
Next Document: Diffusion-weighted MRI in 300 patients presenting late with subacute transient ischemic attack or mi...