RGD Reference Report - Regulation of endothelial nitric oxide synthase by agmatine after transient global cerebral ischemia in rat brain. - Rat Genome Database

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Regulation of endothelial nitric oxide synthase by agmatine after transient global cerebral ischemia in rat brain.

Authors: Mun, CH  Lee, WT  Park, KA  Lee, JE 
Citation: Mun CH, etal., Anat Cell Biol. 2010 Sep;43(3):230-40. Epub 2010 Sep 30.
RGD ID: 4891961
Pubmed: PMID:21212863   (View Abstract at PubMed)
PMCID: PMC3015041   (View Article at PubMed Central)
DOI: DOI:10.5115/acb.2010.43.3.230   (Journal Full-text)

Nitric oxide (NO) production by endothelial nitric oxide synthase (eNOS) plays a protective role in cerebral ischemia by maintaining vascular permeability, whereas NO derived from neuronal and inducible NOS is neurotoxic and can participate in neuronal damage occurring in ischemia. Matrix metalloproteinases (MMPs) are up-regulated by ischemic injury and degrade the basement membrane if brain vessels to promote cell death and tissue injury. We previously reported that agmatine, synthesized from L-arginine by arginine decarboxylase (ADC) which is expressed in endothelial cells, has shown a direct increased eNOS expression and decreased MMPs expression in bEnd3 cells. But, there are few reports about the regulation of eNOS by agmatine in ischemic animal model. In the present study, we examined the expression of eNOS and MMPs by agmatine treatment after transient global ischemia in vivo. Global ischemia was induced with four vessel occlusion (4-VO) and agmatine (100 mg/kg) was administered intraperitoneally at the onset of reperfusion. The animals were euthanized at 6 and 24 hours after global ischemia and prepared for other analysis. Global ischemia led severe neuronal damage in the rat hippocampus and cerebral cortex, but agmatine treatment protected neurons from ischemic injury. Moreover, the level and expression of eNOS was increased by agmatine treatment, whereas inducible NOS (iNOS) and MMP-9 protein expressions were decreased in the brain. These results suggest that agmatine protects microvessels in the brain by activation eNOS as well as reduces extracellular matrix degradation during the early phase of ischemic insult.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
brain ischemia  ISONos3 (Rattus norvegicus)4891961; 4891961 RGD 
brain ischemia  IDA 4891961 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nos3  (nitric oxide synthase 3)

Genes (Mus musculus)
Nos3  (nitric oxide synthase 3, endothelial cell)

Genes (Homo sapiens)
NOS3  (nitric oxide synthase 3)


Additional Information