Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/106849
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dc.contributor.authorZhang, Shaoyi-
dc.contributor.authorWang, Yan-
dc.contributor.authorXie, Wei-
dc.contributor.authorHowe, Ethan N W-
dc.contributor.authorBusschaert, Nathalie-
dc.contributor.authorSauvat, Allan-
dc.contributor.authorLeduc, Marion-
dc.contributor.authorSilva, Lígia C. Gomes da-
dc.contributor.authorChen, Guo-
dc.contributor.authorMartins, Isabelle-
dc.contributor.authorDeng, Xiaxing-
dc.contributor.authorMaiuri, Luigi-
dc.contributor.authorKepp, Oliver-
dc.contributor.authorSoussi, Thierry-
dc.contributor.authorGale, Philip A-
dc.contributor.authorZamzami, Naoufal-
dc.contributor.authorKroemer, Guido-
dc.date.accessioned2023-04-27T08:32:12Z-
dc.date.available2023-04-27T08:32:12Z-
dc.date.issued2019-03-11-
dc.identifier.issn2041-4889pt
dc.identifier.urihttps://hdl.handle.net/10316/106849-
dc.description.abstractCystic fibrosis is a disease caused by defective function of a chloride channel coupled to a blockade of autophagic flux. It has been proposed to use synthetic chloride transporters as pharmacological agents to compensate insufficient chloride fluxes. Here, we report that such chloride anionophores block autophagic flux in spite of the fact that they activate the pro-autophagic transcription factor EB (TFEB) coupled to the inhibition of the autophagy-suppressive mTORC1 kinase activity. Two synthetic chloride transporters (SQ1 and SQ2) caused a partially TFEB-dependent relocation of the autophagic marker LC3 to the Golgi apparatus. Inhibition of TFEB activation using a calcium chelator or calcineurin inhibitors reduced the formation of LC3 puncta in cells, yet did not affect the cytotoxic action of SQ1 and SQ2 that could be observed after prolonged incubation. In conclusion, the squaramide-based synthetic chloride transporters studied in this work (which can also dissipate pH gradients) are probably not appropriate for the treatment of cystic fibrosis yet might be used for other indications such as cancer.pt
dc.language.isoengpt
dc.publisherSpringer Naturept
dc.relationS.Z., Y.W., W.X. are supported by the China Scholarship Council. G.K. is supported by the Ligue contre le Cancer (équipes labelisées); Agence National de la Recherche (ANR)— Projets blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de- France; Institut National du Cancer (INCa); Fondation Bettencourt-Schueller; Fondation de France; Fondation pour la Recherche Médicale (FRM); the European Commission (ArtForce); the LabEx Immuno-Oncology; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and the SIRIC Cancer Research and Personalized Medicine (CARPEM). P.A.G. is supported by the Australian Research Council (DP180100612).pt
dc.rightsopenAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt
dc.subject.meshAutophagypt
dc.subject.meshBasic Helix-Loop-Helix Leucine Zipper Transcription Factorspt
dc.subject.meshCell Deathpt
dc.subject.meshCell Line, Tumorpt
dc.subject.meshGolgi Apparatuspt
dc.subject.meshHumanspt
dc.subject.meshHydrocarbons, Fluorinatedpt
dc.subject.meshIon Transportpt
dc.subject.meshMicrotubule-Associated Proteinspt
dc.subject.meshPhosphorylationpt
dc.subject.meshReactive Oxygen Speciespt
dc.subject.meshTOR Serine-Threonine Kinasespt
dc.subject.meshUp-Regulationpt
dc.titleSquaramide-based synthetic chloride transporters activate TFEB but block autophagic fluxpt
dc.typearticle-
degois.publication.firstPage242pt
degois.publication.issue3pt
degois.publication.titleCell Death and Diseasept
dc.peerreviewedyespt
dc.identifier.doi10.1038/s41419-019-1474-8pt
degois.publication.volume10pt
dc.date.embargo2019-03-11*
uc.date.periodoEmbargo0pt
item.cerifentitytypePublications-
item.languageiso639-1en-
item.fulltextCom Texto completo-
item.grantfulltextopen-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.openairetypearticle-
crisitem.author.researchunitCQC - Coimbra Chemistry Centre-
crisitem.author.parentresearchunitFaculty of Sciences and Technology-
crisitem.author.orcid0000-0003-0624-8819-
Appears in Collections:FCTUC Química - Artigos em Revistas Internacionais
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