dc.date.accessioned | 2019-01-07T11:52:22Z | |
dc.date.available | 2019-01-07T11:52:22Z | |
dc.date.created | 2018-06-22T12:50:28Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Vardjan, Nina Chowdhury, Helena H. Horvat, Anemari Velebit, Jelena Malnar, Maja Muhic, Marko Kreft, Marko Krivec, Spela G. Bobnar, Sasa T. Mis, Katarina Pirkmajer, Sergej Offermanns, Stefan Henriksen, Gjermund Storm-Mathisen, Jon Bergersen, Linda Hildegard Zorec, Robert . Enhancement of astroglial aerobic glycolysis by extracellular lactate-mediated increase in cAMP. Frontiers in Molecular Neuroscience. 2018, 11 | |
dc.identifier.uri | http://hdl.handle.net/10852/66029 | |
dc.description.abstract | Besides being a neuronal fuel, L-lactate is also a signal in the brain. Whether extracellular L-lactate affects brain metabolism, in particular astrocytes, abundant neuroglial cells, which produce L-lactate in aerobic glycolysis, is unclear. Recent studies suggested that astrocytes express low levels of the L-lactate GPR81 receptor (EC50 ≈ 5 mM) that is in fat cells part of an autocrine loop, in which the Gi-protein mediates reduction of cytosolic cyclic adenosine monophosphate (cAMP). To study whether a similar signaling loop is present in astrocytes, affecting aerobic glycolysis, we measured the cytosolic levels of cAMP, D-glucose and L-lactate in single astrocytes using fluorescence resonance energy transfer (FRET)-based nanosensors. In contrast to the situation in fat cells, stimulation by extracellular L-lactate and the selective GPR81 agonists, 3-chloro-5-hydroxybenzoic acid (3Cl-5OH-BA) or 4-methyl-N-(5-(2-(4-methylpiperazin-1-yl)-2-oxoethyl)-4-(2-thienyl)-1,3-thiazol-2-yl)cyclohexanecarboxamide (Compound 2), like adrenergic stimulation, elevated intracellular cAMP and L-lactate in astrocytes, which was reduced by the inhibition of adenylate cyclase. Surprisingly, 3Cl-5OH-BA and Compound 2 increased cytosolic cAMP also in GPR81-knock out astrocytes, indicating that the effect is GPR81-independent and mediated by a novel, yet unidentified, excitatory L-lactate receptor-like mechanism in astrocytes that enhances aerobic glycolysis and L-lactate production via a positive feedback mechanism. | en_US |
dc.language | EN | |
dc.publisher | Frontiers Media | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Enhancement of astroglial aerobic glycolysis by extracellular lactate-mediated increase in cAMP | en_US |
dc.title.alternative | ENEngelskEnglishEnhancement of astroglial aerobic glycolysis by extracellular lactate-mediated increase in cAMP | |
dc.type | Journal article | en_US |
dc.creator.author | Vardjan, Nina | |
dc.creator.author | Chowdhury, Helena H. | |
dc.creator.author | Horvat, Anemari | |
dc.creator.author | Velebit, Jelena | |
dc.creator.author | Malnar, Maja | |
dc.creator.author | Muhic, Marko | |
dc.creator.author | Kreft, Marko | |
dc.creator.author | Krivec, Spela G. | |
dc.creator.author | Bobnar, Sasa T. | |
dc.creator.author | Mis, Katarina | |
dc.creator.author | Pirkmajer, Sergej | |
dc.creator.author | Offermanns, Stefan | |
dc.creator.author | Henriksen, Gjermund | |
dc.creator.author | Storm-Mathisen, Jon | |
dc.creator.author | Bergersen, Linda Hildegard | |
dc.creator.author | Zorec, Robert | |
cristin.unitcode | 185,15,4,20 | |
cristin.unitname | Kjerne- og energifysikk | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1593250 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Frontiers in Molecular Neuroscience&rft.volume=11&rft.spage=&rft.date=2018 | |
dc.identifier.jtitle | Frontiers in Molecular Neuroscience | |
dc.identifier.volume | 11 | |
dc.identifier.doi | http://dx.doi.org/10.3389/fnmol.2018.00148 | |
dc.identifier.urn | URN:NBN:no-68538 | |
dc.type.document | Tidsskriftartikkel | en_US |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 1662-5099 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/66029/1/1593250.pdf | |
dc.type.version | PublishedVersion | |