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dc.contributor.authorMartin, Pamela M
dc.contributor.authorAnanth, Sudha
dc.contributor.authorCresci, Gail A.
dc.contributor.authorRoon, Penny
dc.contributor.authorSmith, Sylvia B
dc.contributor.authorGanapathy, Vadivel
dc.date.accessioned2010-09-24T22:03:26Z
dc.date.available2010-09-24T22:03:26Z
dc.date.issued2009-02-19en_US
dc.identifier.citationMol Vis. 2009 Feb 16; 15:362-372en_US
dc.identifier.issn1090-0535en_US
dc.identifier.pmid19223991en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/143
dc.description.abstractPURPOSE: GPR109A has been identified as a G-protein-coupled receptor for niacin. beta-hydroxybutyrate (beta-HB) is a physiologic ligand for the receptor. beta-HB, the predominate ketone body in circulation, is an important energy source for neurons, including retinal neurons, under various physiologic and pathologic conditions. The identification of GPR109A as the receptor for beta-HB suggests additional, hitherto unknown, functions for this metabolite. The circulating levels of beta-HB increase in diabetes. Since retinopathy is a serious complication associated with diabetes, we investigated GPR109A expression in retina and in different retinal cell types to determine if the receptor may have a role in the pathophysiology of diabetic retinopathy. METHODS: RT-PCR, fluorescent in situ hybridization, and immunofluorescent techniques were used to analyze GPR109A expression in mouse retina and in three transformed retinal cell lines: ARPE-19 (RPE), RGC-5 (ganglion), and rMC-1 (M?�ller). Activation of GPR109A by niacin and beta-HB was demonstrated in ARPE-19 cells by cAMP assay. RESULTS: Studies conducted using mouse retinal tissues demonstrated that GPR109A is expressed in retina with its expression restricted to RPE, where it differentially polarizes to the basolateral membrane. These results were confirmed with cell lines, which demonstrated GPR109A expression in ARPE-19, but not in rMC-1 and RGC-5 cells. Primary cultures of mouse RPE also showed robust expression of GPR109A. cAMP assay demonstrated that GPR109A expressed in RPE is functional. CONCLUSIONS: These data represent the first report on GPR109A expression in retina. The exclusive expression of GPR109A in RPE basolateral membrane, which has access to beta-HB in blood, may have biologic importance in diabetic retinopathy.
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshAnimalsen_US
dc.subject.meshCell Line, Transformeden_US
dc.subject.meshCyclic AMP / metabolismen_US
dc.subject.meshFluorescent Antibody Techniqueen_US
dc.subject.meshGene Expression / physiologyen_US
dc.subject.meshHumansen_US
dc.subject.meshIn Situ Hybridization, Fluorescenceen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred BALB Cen_US
dc.subject.meshRNA, Messenger / genetics / metabolismen_US
dc.subject.meshRatsen_US
dc.subject.meshReceptors, G-Protein-Coupled / genetics / metabolismen_US
dc.subject.meshReceptors, Nicotinic / genetics / metabolismen_US
dc.subject.meshRetina / metabolismen_US
dc.subject.meshRetinal Pigment Epithelium / metabolismen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.titleExpression and localization of GPR109A (PUMA-G/HM74A) mRNA and protein in mammalian retinal pigment epithelium.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, N.I.H., Extramuralen_US
dc.identifier.pmcidPMC2642846en_US
dc.contributor.corporatenameDepartment of Biochemistry and Molecular Biologyen_US
dc.contributor.corporatenameDepartment of Cellular Biology and Anatomyen_US
dc.contributor.corporatenameDepartment of Ophthalmologyen_US
dc.contributor.corporatenameDepartment of Surgeryen_US
refterms.dateFOA2019-04-09T16:27:01Z
html.description.abstractPURPOSE: GPR109A has been identified as a G-protein-coupled receptor for niacin. beta-hydroxybutyrate (beta-HB) is a physiologic ligand for the receptor. beta-HB, the predominate ketone body in circulation, is an important energy source for neurons, including retinal neurons, under various physiologic and pathologic conditions. The identification of GPR109A as the receptor for beta-HB suggests additional, hitherto unknown, functions for this metabolite. The circulating levels of beta-HB increase in diabetes. Since retinopathy is a serious complication associated with diabetes, we investigated GPR109A expression in retina and in different retinal cell types to determine if the receptor may have a role in the pathophysiology of diabetic retinopathy. METHODS: RT-PCR, fluorescent in situ hybridization, and immunofluorescent techniques were used to analyze GPR109A expression in mouse retina and in three transformed retinal cell lines: ARPE-19 (RPE), RGC-5 (ganglion), and rMC-1 (M?�ller). Activation of GPR109A by niacin and beta-HB was demonstrated in ARPE-19 cells by cAMP assay. RESULTS: Studies conducted using mouse retinal tissues demonstrated that GPR109A is expressed in retina with its expression restricted to RPE, where it differentially polarizes to the basolateral membrane. These results were confirmed with cell lines, which demonstrated GPR109A expression in ARPE-19, but not in rMC-1 and RGC-5 cells. Primary cultures of mouse RPE also showed robust expression of GPR109A. cAMP assay demonstrated that GPR109A expressed in RPE is functional. CONCLUSIONS: These data represent the first report on GPR109A expression in retina. The exclusive expression of GPR109A in RPE basolateral membrane, which has access to beta-HB in blood, may have biologic importance in diabetic retinopathy.


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