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dc.date.accessioned2020-06-08T18:26:42Z
dc.date.available2020-06-08T18:26:42Z
dc.date.created2019-07-11T12:56:13Z
dc.date.issued2019
dc.identifier.citationVohra, Rupali Aldana, Blanca I Waagepetersen, Helle Bergersen, Linda Hildegard Kolko, Miriam . Dual properties of lactate in muller cells: The effect of GPR81 activation. Investigative Ophthalmology and Visual Science. 2019, 60(4), 999-1008
dc.identifier.urihttp://hdl.handle.net/10852/76801
dc.description.abstractPurpose: Besides being actively metabolized, lactate may also function as a signaling molecule by activation of the G-protein–coupled receptor 81 (GPR81). Thus, we aimed to characterize the metabolic effects of GPR81 activation in Müller cells. Method: Primary Müller cells from mice were treated with and without 10 mM L-lactate in the presence or absence of 6 mM glucose. The effects of lactate receptor GPR81 activation were evaluated by the addition of 5 mM 3,5-DHBA (3,5-dihydroxybenzoic acid), a GPR81 agonist. Western blot analyses were used to determine protein expression of GPR81. Cell survival was assessed through 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) viability assays. Lactate release was quantified by commercially available lactate kits. 13C-labeling studies via mass spectroscopy and Seahorse analyses were performed to evaluate metabolism of lactate and glucose, and mitochondrial function. Finally, Müller cell function was evaluated by measuring glutamate uptake. Results: The lactate receptor, GPR81, was upregulated during glucose deprivation. Treatment with a GPR81 agonist did not affect Müller cell survival. However, GPR81 activation diminished lactate release allowing lactate to be metabolized intracellularly. Furthermore, GPR81 activation increased metabolism of glucose and mitochondrial function. Finally, maximal glutamate uptake decreased in response to GPR81 activation during glucose deprivation. Conclusions: The present study revealed dual properties of lactate via functioning as an active metabolic energy substrate and a regulatory molecule by activation of the GPR81 receptor in primary Müller cells. Thus, combinational therapy of lactate and GPR81 agonists may be of future interest in maintaining Müller cell survival, ultimately leading to increased resistance toward retinal neurodegeneration.
dc.languageEN
dc.publisherLippincott-Raven Publishers
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleDual properties of lactate in muller cells: The effect of GPR81 activation
dc.typeJournal article
dc.creator.authorVohra, Rupali
dc.creator.authorAldana, Blanca I
dc.creator.authorWaagepetersen, Helle
dc.creator.authorBergersen, Linda Hildegard
dc.creator.authorKolko, Miriam
cristin.unitcode185,16,15,0
cristin.unitnameInstitutt for oral biologi
cristin.ispublishedtrue
cristin.fulltextpostprint
cristin.qualitycode2
dc.identifier.cristin1711261
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Investigative Ophthalmology and Visual Science&rft.volume=60&rft.spage=999&rft.date=2019
dc.identifier.jtitleInvestigative Ophthalmology and Visual Science
dc.identifier.volume60
dc.identifier.issue4
dc.identifier.doihttps://doi.org/10.1167/iovs.18-25458
dc.identifier.urnURN:NBN:no-79906
dc.type.documentTidsskriftartikkel
dc.type.peerreviewedPeer reviewed
dc.source.issn0146-0404
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/76801/5/i1552-5783-60-4-999.pdf
dc.type.versionPublishedVersion
cristin.articleid999


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