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The endocannabinoid 2-arachidonoylglycerol promotes endoplasmic reticulum stress in placental cells

2020-08Journal article Open access
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dc.contributor.authorAlmada, Marta
dc.contributor.authorCosta, Lia
dc.contributor.authorFonseca, Bruno
dc.contributor.authorAlves, Patrícia
dc.contributor.authorBraga, Jorge
dc.contributor.authorGonçalves, Daniela
dc.contributor.authorTeixeira, Natércia
dc.contributor.authorCorreia-da-Silva, Georgina
dc.date.accessioned2021-05-20T14:02:29Z
dc.date.available2021-05-20T14:02:29Z
dc.date.issued2020-08
dc.description.abstractProliferation, differentiation and apoptosis of trophoblast cells are required for normal placental development. Impairment of those processes may lead to pregnancy-related diseases. Disruption of endoplasmic reticulum (ER) homeostasis has been associated with several reproductive pathologies including recurrent pregnancy loss and preeclampsia. In the unfolded protein response (UPR), specific ER-stress signalling pathways are activated to restore ER homeostasis, but if the adaptive response fails, apoptosis is triggered. Protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1) and Activating transcription factor 6 (ATF6) are central players in UPR and in ER-stress-induced apoptosis, as well as downstream transcription factors, as C/EBP homologous protein (CHOP). Our previous studies have shown that the endocannabinoid 2-arachidonoylglycerol (2-AG) modulates trophoblast cell turnover. Nevertheless, the role of ER-stress on 2-AG induced apoptosis and cannabinoid signalling in trophoblast has never been addressed. In this work, we used BeWo cells and human primary cytotrophoblasts isolated from term-placenta. The expression of ER-stress markers was analysed by qRT-PCR and Western blotting. ROS generation was assessed by fluorometric methods, while apoptosis was detected by the evaluation of caspase -3/-7 activities and Poly (ADP-ribose) polymerase (PARP) cleavage. Our findings indicate that 2-AG is able to induce ER-stress and apoptosis. Moreover, the eukaryotic initiation factor 2 (eIF2α)/CHOP pathway involved in ER-stress-induced apoptosis is triggered through a mechanism dependent on cannabinoid receptor CB2 activation. The results bring novel insights on the importance of ER-stress and cannabinoid signalling on 2-AG mechanisms of action in placenta.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAlmada M, Costa L, Fonseca B, Alves P, Braga J, Gonçalves D, Teixeira N, Correia-da-Silva G. The endocannabinoid 2-arachidonoylglycerol promotes endoplasmic reticulum stress in placental cells. Reproduction. 2020 Aug;160(2):171-180. doi: 10.1530/REP-19-0539. PMID: 32357311; PMCID: PMC7354702.pt_PT
dc.identifier.doi10.1530/REP-19-0539pt_PT
dc.identifier.issn1470-1626
dc.identifier.urihttp://hdl.handle.net/10400.16/2455
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBioScientificapt_PT
dc.relation.publisherversionhttps://rep.bioscientifica.com/view/journals/rep/160/2/REP-19-0539.xmlpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleThe endocannabinoid 2-arachidonoylglycerol promotes endoplasmic reticulum stress in placental cellspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceEnglandpt_PT
oaire.citation.endPage180pt_PT
oaire.citation.issue2pt_PT
oaire.citation.startPage171pt_PT
oaire.citation.titleReproduction (Cambridge, England)pt_PT
oaire.citation.volume160pt_PT
person.familyNameBraga
person.givenNameJorge
person.identifier.orcid0000-0003-2548-7751
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication310cfe2b-bcef-49bb-b970-11d8993776ec
relation.isAuthorOfPublication.latestForDiscovery310cfe2b-bcef-49bb-b970-11d8993776ec

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