CHIR99021 causes inactivation of Tyrosine Hydroxylase and depletion of dopamine in rat brain striatum
Dopamina; Estriat; Tirosina hidroxilasa
| Autores: | , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:11351/10972 |
| Acceso en línea: | https://hdl.handle.net/11351/10972 http://hdl.handle.net/11351/10972 |
| Access Level: | acceso abierto |
| Palabra clave: | Rates (Animals de laboratori) Sistema nerviós - Degeneració - Tractament Dopamina CHEMICALS AND DRUGS::Macromolecular Substances::Multiprotein Complexes::Axin Signaling Complex::Glycogen Synthase Kinase 3::Glycogen Synthase Kinase 3 beta Other subheadings::Other subheadings::Other subheadings::/antagonists & inhibitors CHEMICALS AND DRUGS::Organic Chemicals::Amines::Biogenic Amines::Biogenic Monoamines::Dopamine DISEASES::Nervous System Diseases::Neurodegenerative Diseases ORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice COMPUESTOS QUÍMICOS Y DROGAS::sustancias macromoleculares::complejos multiproteicos::complejo de señalización axin::glucógeno sintasa cinasa 3::glucógeno sintasa cinasa 3 beta Otros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidores COMPUESTOS QUÍMICOS Y DROGAS::compuestos orgánicos::aminas::aminas biógenas::monoaminas biógenas::dopamina ENFERMEDADES::enfermedades del sistema nervioso::enfermedades neurodegenerativas ORGANISMOS::Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratas |
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CHIR99021 causes inactivation of Tyrosine Hydroxylase and depletion of dopamine in rat brain striatum |
| title |
CHIR99021 causes inactivation of Tyrosine Hydroxylase and depletion of dopamine in rat brain striatum |
| spellingShingle |
CHIR99021 causes inactivation of Tyrosine Hydroxylase and depletion of dopamine in rat brain striatum Hamdon, Sally Rates (Animals de laboratori) Sistema nerviós - Degeneració - Tractament Dopamina CHEMICALS AND DRUGS::Macromolecular Substances::Multiprotein Complexes::Axin Signaling Complex::Glycogen Synthase Kinase 3::Glycogen Synthase Kinase 3 beta Other subheadings::Other subheadings::Other subheadings::/antagonists & inhibitors CHEMICALS AND DRUGS::Organic Chemicals::Amines::Biogenic Amines::Biogenic Monoamines::Dopamine DISEASES::Nervous System Diseases::Neurodegenerative Diseases ORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice COMPUESTOS QUÍMICOS Y DROGAS::sustancias macromoleculares::complejos multiproteicos::complejo de señalización axin::glucógeno sintasa cinasa 3::glucógeno sintasa cinasa 3 beta Otros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidores COMPUESTOS QUÍMICOS Y DROGAS::compuestos orgánicos::aminas::aminas biógenas::monoaminas biógenas::dopamina ENFERMEDADES::enfermedades del sistema nervioso::enfermedades neurodegenerativas ORGANISMOS::Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratas |
| title_short |
CHIR99021 causes inactivation of Tyrosine Hydroxylase and depletion of dopamine in rat brain striatum |
| title_full |
CHIR99021 causes inactivation of Tyrosine Hydroxylase and depletion of dopamine in rat brain striatum |
| title_fullStr |
CHIR99021 causes inactivation of Tyrosine Hydroxylase and depletion of dopamine in rat brain striatum |
| title_full_unstemmed |
CHIR99021 causes inactivation of Tyrosine Hydroxylase and depletion of dopamine in rat brain striatum |
| title_sort |
CHIR99021 causes inactivation of Tyrosine Hydroxylase and depletion of dopamine in rat brain striatum |
| dc.creator.none.fl_str_mv |
Hamdon, Sally Fernandez, Pol Omar, Muhammad Yusof González Sepúlveda, Marta Ortiz, Jordi Gil, Carles |
| author |
Hamdon, Sally |
| author_facet |
Hamdon, Sally Fernandez, Pol Omar, Muhammad Yusof González Sepúlveda, Marta Ortiz, Jordi Gil, Carles |
| author_role |
author |
| author2 |
Fernandez, Pol Omar, Muhammad Yusof González Sepúlveda, Marta Ortiz, Jordi Gil, Carles |
| author2_role |
author author author author author |
| dc.contributor.none.fl_str_mv |
Institut Català de la Salut [Hamdon S, Omar MY, Gil C] Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Spain. Institut de Neurociències, Universitat Autònoma de Barcelona, Spain. [Fernandez-Gonzalez P] Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Spain. [González-Sepúlveda M] Grup de Recerca de Malalties Neurodegeneratives, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain. Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, USA. [Ortiz J] Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Spain. Institut de Neurociències, Universitat Autònoma de Barcelona, Spain. Centro Investigación Biomédica en Red de Salud Mental, CIBERSAM, and Translational Neuroscience Unit, Parc Taulí University Hospital and Universitat Autònoma de Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus |
| dc.subject.none.fl_str_mv |
Rates (Animals de laboratori) Sistema nerviós - Degeneració - Tractament Dopamina CHEMICALS AND DRUGS::Macromolecular Substances::Multiprotein Complexes::Axin Signaling Complex::Glycogen Synthase Kinase 3::Glycogen Synthase Kinase 3 beta Other subheadings::Other subheadings::Other subheadings::/antagonists & inhibitors CHEMICALS AND DRUGS::Organic Chemicals::Amines::Biogenic Amines::Biogenic Monoamines::Dopamine DISEASES::Nervous System Diseases::Neurodegenerative Diseases ORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice COMPUESTOS QUÍMICOS Y DROGAS::sustancias macromoleculares::complejos multiproteicos::complejo de señalización axin::glucógeno sintasa cinasa 3::glucógeno sintasa cinasa 3 beta Otros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidores COMPUESTOS QUÍMICOS Y DROGAS::compuestos orgánicos::aminas::aminas biógenas::monoaminas biógenas::dopamina ENFERMEDADES::enfermedades del sistema nervioso::enfermedades neurodegenerativas ORGANISMOS::Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratas |
| topic |
Rates (Animals de laboratori) Sistema nerviós - Degeneració - Tractament Dopamina CHEMICALS AND DRUGS::Macromolecular Substances::Multiprotein Complexes::Axin Signaling Complex::Glycogen Synthase Kinase 3::Glycogen Synthase Kinase 3 beta Other subheadings::Other subheadings::Other subheadings::/antagonists & inhibitors CHEMICALS AND DRUGS::Organic Chemicals::Amines::Biogenic Amines::Biogenic Monoamines::Dopamine DISEASES::Nervous System Diseases::Neurodegenerative Diseases ORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::Mice COMPUESTOS QUÍMICOS Y DROGAS::sustancias macromoleculares::complejos multiproteicos::complejo de señalización axin::glucógeno sintasa cinasa 3::glucógeno sintasa cinasa 3 beta Otros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidores COMPUESTOS QUÍMICOS Y DROGAS::compuestos orgánicos::aminas::aminas biógenas::monoaminas biógenas::dopamina ENFERMEDADES::enfermedades del sistema nervioso::enfermedades neurodegenerativas ORGANISMOS::Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratas |
| description |
Dopamina; Estriat; Tirosina hidroxilasa |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2024 2024 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/11351/10972 http://hdl.handle.net/11351/10972 |
| url |
https://hdl.handle.net/11351/10972 http://hdl.handle.net/11351/10972 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Neuropharmacology;242 https://doi.org/10.1016/j.neuropharm.2023.109759 |
| dc.rights.none.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier |
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Elsevier |
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Scientia reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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1869418153577021440 |
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CHIR99021 causes inactivation of Tyrosine Hydroxylase and depletion of dopamine in rat brain striatumHamdon, SallyFernandez, PolOmar, Muhammad YusofGonzález Sepúlveda, MartaOrtiz, JordiGil, CarlesRates (Animals de laboratori)Sistema nerviós - Degeneració - TractamentDopaminaCHEMICALS AND DRUGS::Macromolecular Substances::Multiprotein Complexes::Axin Signaling Complex::Glycogen Synthase Kinase 3::Glycogen Synthase Kinase 3 betaOther subheadings::Other subheadings::Other subheadings::/antagonists & inhibitorsCHEMICALS AND DRUGS::Organic Chemicals::Amines::Biogenic Amines::Biogenic Monoamines::DopamineDISEASES::Nervous System Diseases::Neurodegenerative DiseasesORGANISMS::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Eutheria::Rodentia::Muridae::Murinae::MiceCOMPUESTOS QUÍMICOS Y DROGAS::sustancias macromoleculares::complejos multiproteicos::complejo de señalización axin::glucógeno sintasa cinasa 3::glucógeno sintasa cinasa 3 betaOtros calificadores::Otros calificadores::Otros calificadores::/antagonistas & inhibidoresCOMPUESTOS QUÍMICOS Y DROGAS::compuestos orgánicos::aminas::aminas biógenas::monoaminas biógenas::dopaminaENFERMEDADES::enfermedades del sistema nervioso::enfermedades neurodegenerativasORGANISMOS::Eukaryota::animales::Chordata::vertebrados::mamíferos::Eutheria::Rodentia::Muridae::Murinae::ratasDopamina; Estriat; Tirosina hidroxilasaDopamina; Estriado; Tirosina hidroxilasaDopamine; Striatum; Tyrosine hydroxylaseCHIR99021, also known as laduviglusib or CT99021, is a Glycogen-synthase kinase 3β (GSK3β) inhibitor, which has been reported as a promising drug for cardiomyocyte regeneration or treatment of sensorial hearing loss. Since the activation of dopamine (DA) receptors regulates dopamine synthesis and they can signal through the β-arrestin pathway and GSK3β, we decided to check the effect of GSK3β inhibitors (CHIR99021, SB216763 and lithium ion) on the control of DA synthesis. Using ex vivo experiments with minces from rat brain striatum, we observed that CHIR99021, but not SB216763 or lithium, causes complete abrogation of both DA synthesis and accumulation, pointing to off-target effects of CHIR99021. This decrease can be attributed to tyrosine hydroxylase (TH) inhibition since the accumulation of l-DOPA in the presence of a DOPA decarboxylase inhibitor was similarly decreased. On the other hand, CHIR99021 caused a dramatic increase in the DOPAC/DA ratio, an indicator of DA metabolization, and hindered DA incorporation into striatum tissue. Tetrabenazine, an inhibitor of DA vesicular transport, also caused DA depletion and DOPAC/DA ratio increase to the same extent as CHIR99021. In addition, both CHIR99021 or SB216763, but not lithium, decreased TH phosphorylation in Ser19, but not in Ser31 or Ser40. These results demonstrate that CHIR99021 can lead to TH inactivation and DA depletion in brain striatum, opening the possibility of its use in DA-related disorders, and shows effects to be considered in future clinical trials. More work is needed to find the mechanism exerted by CHIR99021 on DA accumulation.This work was supported by Spanish Government grant SAF2017-87199-R. S.H. received a predoctoral fellowship from the Universitat Autònoma de Barcelona.ElsevierInstitut Català de la Salut[Hamdon S, Omar MY, Gil C] Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Spain. Institut de Neurociències, Universitat Autònoma de Barcelona, Spain. [Fernandez-Gonzalez P] Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Spain. [González-Sepúlveda M] Grup de Recerca de Malalties Neurodegeneratives, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain. Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, USA. [Ortiz J] Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Spain. Institut de Neurociències, Universitat Autònoma de Barcelona, Spain. Centro Investigación Biomédica en Red de Salud Mental, CIBERSAM, and Translational Neuroscience Unit, Parc Taulí University Hospital and Universitat Autònoma de Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/10972http://hdl.handle.net/11351/10972Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNeuropharmacology;242https://doi.org/10.1016/j.neuropharm.2023.109759Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/109722026-05-29T05:05:01Z |
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