Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics
dc.contributor.author | Ruso Julve, Fulgencio | |
dc.contributor.author | Pombero, Ana | |
dc.contributor.author | Pilar Cuéllar, Fuencisla | |
dc.contributor.author | García Díaz, Nuria | |
dc.contributor.author | Garcia López, Raquel | |
dc.contributor.author | Juncal Ruiz, María | |
dc.contributor.author | Castro, Elena | |
dc.contributor.author | Díaz, Álvaro | |
dc.contributor.author | Vazquez Bourgón, Javier | |
dc.contributor.author | García Blanco, Agustín | |
dc.contributor.author | Garro Martínez, Emilio | |
dc.contributor.author | Pisonero, Helena | |
dc.contributor.author | Estirado, Alicia | |
dc.contributor.author | Ayesa Arriola, Rosa | |
dc.contributor.author | López Giménez, Juan | |
dc.contributor.author | Mayor, Federico | |
dc.contributor.author | Valdizán, Elsa | |
dc.contributor.author | Meana Martínez, José Javier ![]() | |
dc.contributor.author | González Maeso, Javier | |
dc.contributor.author | Martínez, Salvador | |
dc.contributor.author | Vaqué, José Pedro | |
dc.contributor.author | Crespo Facorro, Benedicto | |
dc.date.accessioned | 2020-02-28T13:34:28Z | |
dc.date.available | 2020-02-28T13:34:28Z | |
dc.date.issued | 2019-11-18 | |
dc.identifier.citation | Translational Psychiatry 9 : (2019) // Article ID 306 | es_ES |
dc.identifier.issn | 2158-3188 | |
dc.identifier.uri | http://hdl.handle.net/10810/41860 | |
dc.description.abstract | A better understanding of the molecular mechanisms that participate in the development and clinical manifestations of schizophrenia can lead to improve our ability to diagnose and treat this disease. Previous data strongly associated the levels of deregulated ADAMTS2 expression in peripheral blood mononuclear cells (PBMCs) from patients at first episode of psychosis (up) as well as in clinical responders to treatment with antipsychotic drugs (down). In this current work, we performed an independent validation of such data and studied the mechanisms implicated in the control of ADAMTS2 gene expression. Using a new cohort of drug-na)Ve schizophrenia patients with clinical follow-up, we confirmed that the expression of ADAMTS2 was highly upregulated in PBMCs at the onset (drug-naive patients) and downregulated, in clinical responders, after treatment with antipsychotics. Mechanistically, ADAMTS2 expression was activated by dopaminergic signalling (D-1-class receptors) and downstream by cAMP/CREB and mitogen-activated protein kinase (MAPK)/ERK signalling. Incubation with antipsychotic drugs and selective PKA and MEK inhibitors abrogated D-1-mediated activation of ADAMTS2 in neuronal-like cells. Thus, D-1 receptors signalling towards CREB activation might participate in the onset and clinical responses to therapy in schizophrenia patients, by controlling ADAMTS2 expression and activity. The unbiased investigation of molecular mechanisms triggered by antipsychotic drugs may provide a new landscape of novel targets potentially associated with clinical efficacy. | es_ES |
dc.description.sponsorship | We are highly indebted to the participants and their families for their cooperation in this study. We also thank IDIVAL biobank (Ines Santiuste and Jana Arozamena) for clinical samples and data as well as the PAFIP members (Marga Corredera) for the data collection. This work was supported by: SAF2016-76046-R and SAF2013-46292-R (MINECO and FEDER) to B.C.F., PI16/00156 (isciii and FEDER) to J.P.V., LUCHAMOS POR LA VIDA project to F.R.J. and J.P.V., SAF2017-83702-R (MINECO and FEDER), Red TERCEL RD12/0019/0024 (ISCIII) and GVA-PROMETEO 2018/041 (Generalitat Valenciana) to S.M. J.P.V. supported by the RyC research programme (RYC-2013-14097) and F.R.J. by the predoctoral research programme (BES-2014-070615), from MINECO and FEDER. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/Red TERCEL RD12/0019/0024 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/GVA-PROMETEO 2018/041 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | superior temporal cortex | es_ES |
dc.subject | classical neuroleptics | es_ES |
dc.subject | individual variation | es_ES |
dc.subject | 5-ht2a receptor | es_ES |
dc.subject | tegmental area | es_ES |
dc.subject | clozapine | es_ES |
dc.subject | schizophrenia | es_ES |
dc.subject | drugs | es_ES |
dc.subject | refractoriness | es_ES |
dc.subject | sensitivity | es_ES |
dc.title | Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution andreproductionin any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a linktotheCreativeCommons license,and indicate ifchanges were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicatedotherwise in a credit line to the material. Ifmaterial is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtainpermission directly from the copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.nature.com/articles/s41398-019-0647-7 | es_ES |
dc.identifier.doi | 10.1038/s41398-019-0647-7 | |
dc.departamentoes | Farmacología | es_ES |
dc.departamentoeu | Farmakologia | es_ES |
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