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dc.rights.licenseopenen_US
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorMIRALPEIX, Cristina
dc.contributor.authorREGUERA, Ana Cristina
dc.contributor.authorFOSCH, Anna
dc.contributor.authorCASAS, Maria
dc.contributor.authorLILLO, Jaume
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorNAVARRO, Gemma
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorFRANCO, Rafael
dc.contributor.authorCASAS, Josefina
dc.contributor.authorALEXANDER, Stephen P.H.
dc.contributor.authorCASALS, Nuria
dc.contributor.authorRODRIGUEZ-RODRIGUEZ, Rosalia
dc.date.accessioned2022-03-09T08:47:44Z
dc.date.available2022-03-09T08:47:44Z
dc.date.issued2021-04
dc.identifier.issn1476-5381en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/136393
dc.description.abstractEnBackground and Purpose : The enzyme α/β-hydrolase domain containing 6 (ABHD6), a new member of the endocannabinoid system, is a promising therapeutic target against neuronal-related diseases. However, how ABHD6 activity is regulated is not known. ABHD6 coexists in protein complexes with the brain-specific carnitine palmitoyltransferase 1C (CPT1C). CPT1C is involved in neuro-metabolic functions, depending on brain malonyl–CoA levels. Our aim was to study CPT1C–ABHD6 interaction and determine whether CPT1C is a key regulator of ABHD6 activity depending on nutritional status. Experimental Approach : Co-immunoprecipitation and FRET assays were used to explore ABHD6 interaction with CPT1C or modified malonyl–CoA-insensitive or C-terminal truncated CPT1C forms. Cannabinoid CB1 receptor-mediated signalling was investigated by determining cAMP levels. A novel highly sensitive fluorescent method was optimized to measure ABHD6 activity in non-neuronal and neuronal cells and in brain tissues from wild-type (WT) and CPT1C–KO mice. Key Results : CPT1C interacted with ABHD6 and negatively regulated its hydrolase activity, thereby regulating 2-AG downstream signalling. Accordingly, brain tissues of CPT1C–KO mice showed increased ABHD6 activity. CPT1C malonyl–CoA sensing was key to the regulatory role on ABHD6 activity and CB1 receptor signalling. Fasting, which attenuates brain malonyl–CoA, significantly increased ABHD6 activity in hypothalamus from WT, but not CPT1C–KO, mice. Conclusions and Implications : Our finding that negative regulation of ABHD6 activity, particularly in the hypothalamus, is sensitive to nutritional status throws new light on the characterization and the importance of the proteins involved as potential targets against diseases affecting the CNS.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.subject.enABHD6
dc.subject.enCPT1C
dc.subject.enendocannabinoid signalling
dc.subject.enfasting
dc.subject.enhippocampus
dc.subject.enhypothalamus
dc.subject.enmalonyl-CoA
dc.title.enCarnitine palmitoyltransferase 1C negatively regulates the endocannabinoid hydrolase ABHD6 in mice, depending on nutritional status
dc.title.alternativeBr J Pharmacolen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1111/bph.15377en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed33444462en_US
bordeaux.journalBritish Journal of Pharmacologyen_US
bordeaux.page1507-1523en_US
bordeaux.volume178en_US
bordeaux.hal.laboratoriesNeurocentre Magendie - UMR-S 1215en_US
bordeaux.issue7en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDFundació la Marató de TV3en_US
bordeaux.identifier.funderIDAgència de Gestió d'Ajuts Universitaris i de Recercaen_US
bordeaux.identifier.funderIDAgencia Estatal de Investigaciónen_US
bordeaux.identifier.funderIDMinisterio de Economía y Competitividaden_US
bordeaux.identifier.funderIDIndiana University Bloomingtonen_US
hal.identifierhal-03602375
hal.version1
hal.date.transferred2022-03-09T08:47:49Z
hal.exporttrue
dc.rights.ccCC BY-NC-SAen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=British%20Journal%20of%20Pharmacology&rft.date=2021-04&rft.volume=178&rft.issue=7&rft.spage=1507-1523&rft.epage=1507-1523&rft.eissn=1476-5381&rft.issn=1476-5381&rft.au=MIRALPEIX,%20Cristina&REGUERA,%20Ana%20Cristina&FOSCH,%20Anna&CASAS,%20Maria&LILLO,%20Jaume&rft.genre=article


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