RGD Reference Report - Enhanced prostacyclin synthesis by adenoviral gene transfer reduced glial activation and ameliorated dopaminergic dysfunction in hemiparkinsonian rats. - Rat Genome Database

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Enhanced prostacyclin synthesis by adenoviral gene transfer reduced glial activation and ameliorated dopaminergic dysfunction in hemiparkinsonian rats.

Authors: Tsai, May-Jywan  Weng, Ching-Feng  Yu, Nien-Chu  Liou, Dann-Ying  Kuo, Fu-San  Huang, Ming-Chao  Huang, Wen-Cheng  Tam, Kabik  Shyue, Song-Kun  Cheng, Henrich 
Citation: Tsai MJ, etal., Oxid Med Cell Longev. 2013;2013:649809. doi: 10.1155/2013/649809. Epub 2013 Apr 3.
RGD ID: 401959749
Pubmed: PMID:23691265   (View Abstract at PubMed)
PMCID: PMC3649752   (View Article at PubMed Central)
DOI: DOI:10.1155/2013/649809   (Journal Full-text)

Prostacyclin (PGI2), a potent vasodilator and platelet antiaggregatory eicosanoid, is cytoprotective in cerebral circulation. It is synthesized from arachidonic acid (AA) by the sequential action of cyclooxygenase- (COX-) 1 or 2 and prostacyclin synthase (PGIS). Because prostacyclin is unstable in vivo, PGI2 analogs have been developed and demonstrated to protect against brain ischemia. This work attempts to selectively augment PGI2 synthesis in mixed glial culture or in a model of Parkinson's disease (PD) by direct adenoviral gene transfer of prostacyclin biosynthetic enzymes and examines whether it confers protection in cultures or in vivo. Confluent mixed glial cultures actively metabolized exogenous AA into PGE2 and PGD2. These PGs were largely NS398 sensitive and considered as COX-2 products. Gene transfer of AdPGIS to the cultures effectively shunted the AA catabolism to prostacyclin synthesis and concurrently reduced cell proliferation. Furthermore, PGIS overexpression significantly reduced LPS stimulation in cultures. In vivo, adenoviral gene transfer of bicistronic COX-1/PGIS to substantia nigra protected 6-OHDA- induced dopamine depletion and ameliorated behavioral deficits. Taken together, this study shows that enhanced prostacyclin synthesis reduced glial activation and ameliorated motor dysfunction in hemiparkinsonian rats. Prostacyclin may have a neuroprotective role in modulating the inflammatory response in degenerating nigra-striatal pathway.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHumanParkinson's disease treatmentIMP human gene in a rat modelRGD 
PtgisRatParkinson's disease treatmentISOPTGIS (Homo sapiens)human gene in a rat modelRGD 
PtgisMouseParkinson's disease treatmentISOPTGIS (Homo sapiens)human gene in a rat modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgis  (prostaglandin I2 synthase)

Genes (Mus musculus)
Ptgis  (prostaglandin I2 (prostacyclin) synthase)

Genes (Homo sapiens)
PTGIS  (prostaglandin I2 synthase)


Additional Information