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Paracrine signaling by glial cell-derived triiodothyronine activates neuronal gene expression in the rodent brain and human cells

dc.creatorFreitas, Beatriz C.G.
dc.creatorGereben, Balázs
dc.creatorCastillo, Melany
dc.creatorKalló, Imre
dc.creatorZeöld, Anikó
dc.creatorEgri, Péter
dc.creatorLiposits, Zsolt
dc.creatorZavacki, Ann Marie
dc.creatorMaciel, Rui M.B.
dc.creatorJo, Sungro
dc.creatorSingru, Praful
dc.creatorSánchez, Edith
dc.creatorLechan, Ronald M.
dc.creatorBianco, Antonio C.
dc.date.accessioned2017-06-30T01:38:06Z
dc.date.available2017-06-30T01:38:06Z
dc.date.issued2010es_ES
dc.identifier1494es_ES
dc.identifier.issn0021-9738es_ES
dc.identifier.urihttp://repositorio.inprf.gob.mx/handle/123456789/6175
dc.identifier.urihttps://doi.org/10.1172/JCI41977es_ES
dc.language.isoenges_ES
dc.relation120 (6) 2206-2217 p.es_ES
dc.relationversión del editores_ES
dc.rightsacceso cerradoes_ES
dc.subject.meshAstrocytes-Metabolismes_ES
dc.subject.meshAnimalses_ES
dc.subject.meshBraines_ES
dc.subject.meshCellses_ES
dc.subject.meshGene Expressiones_ES
dc.subject.meshHypothyroidism-Geneticses_ES
dc.subject.meshIodide Peroxidase-Physiologyes_ES
dc.subject.meshMalees_ES
dc.subject.meshMice-Inbred C57BLes_ES
dc.subject.meshMice-Knockoutes_ES
dc.subject.meshNeurogliaes_ES
dc.subject.meshRats-Sprague-Dawleyes_ES
dc.subject.meshReceptors-Thyroid Hormonees_ES
dc.subject.meshThyroid Hormones-Physiologyes_ES
dc.subject.meshThyroxinees_ES
dc.subject.meshRodentiaes_ES
dc.titleParacrine signaling by glial cell-derived triiodothyronine activates neuronal gene expression in the rodent brain and human cellses_ES
dc.typearticlees_ES
dc.contributor.affiliationLaboratory of Molecular Endocrinology, Division of Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo SP, Braziles_ES
dc.contributor.emailabianco@med.miami.edu.es_ES
dc.relation.jnabreviadoJ CLIN INVESTes_ES
dc.relation.journalThe Journal of Clinical Investigationes_ES
dc.identifier.placeEstados Unidoses_ES
dc.date.published2010es_ES
dc.identifier.organizacionInstituto Nacional de Psiquiatría Ramón de la Fuente Muñizes_ES
dc.identifier.eissn1558-8238es_ES
dc.identifier.doi10.1172/JCI41977es_ES
dc.description.monthJunes_ES
dc.description.abstractotrodiomaHypothyroidism in humans is characterized by severe neurological consequences that are often irreversible, highlighting the critical role of thyroid hormone (TH) in the brain. Despite this, not much is known about the signaling pathways that control TH action in the brain. What is known is that the prohormone thyroxine (T4) is converted to the active hormone triiodothyronine (T3) by type 2 deiodinase (D2) and that this occurs in astrocytes, while TH receptors and type 3 deiodinase (D3), which inactivates T3, are found in adjacent neurons. Here, we modeled TH action in the brain using an in vitro coculture system of D2-expressing H4 human glioma cells and D3-expressing SK-N-AS human neuroblastoma cells. We found that glial cell D2 activity resulted in increased T3 production, which acted in a paracrine fashion to induce T3-responsive genes, including ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), in the cocultured neurons. D3 activity in the neurons modulated these effects. Furthermore, this paracrine pathway was regulated by signals such as hypoxia, hedgehog signaling, and LPS-induced inflammation, as evidenced both in the in vitro coculture system and in in vivo rat models of brain ischemia and mouse models of inflammation. This study therefore presents what we believe to be the first direct evidence for a paracrine loop linking glial D2 activity to TH receptors in neurons, thereby identifying deiodinases as potential control points for the regulation of TH signaling in the brain during health and diseasees_ES
dc.subject.kwRatoneses_ES
dc.subject.kwCerebroes_ES
dc.subject.kwCélulases_ES
dc.subject.kwHumanoses_ES
dc.subject.kwRatases_ES
dc.subject.kwNeuronases_ES
dc.subject.kwTriyodotironinaes_ES
dc.subject.koMicees_ES
dc.subject.koBraines_ES
dc.subject.koCellses_ES
dc.subject.koHumanses_ES
dc.subject.koRatses_ES
dc.subject.koNeuronses_ES
dc.subject.koTriiodothyroninees_ES


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