Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice hypothalamus

Detalhes bibliográficos
Autor(a) principal: Rodrigues, Bárbara de Almeida
Data de Publicação: 2017
Outros Autores: Kuga, Gabriel Keine [UNESP], Muñoz, Vitor Rosetto, Gaspar, Rafael Calais, Tavares, Mariana Rosolen, Botezelli, José Diego, da Silva, Adelino Sanchez Ramos, Cintra, Dennys Esper, de Moura, Leandro Pereira, Simabuco, Fernando Moreira, Ropelle, Eduardo Rochete, Pauli, José Rodrigo
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.neulet.2017.08.067
http://hdl.handle.net/11449/170091
Resumo: The mitogen-activated kinase phosphatase-3 (MKP-3) has gained great importance in the scientific community by acting as a regulator of the cell cycle through dephosphorylation of FoxO1, an important transcription factor involved in the insulin intracellular signaling cascade. When dephosphorylated and translocated to the nuclei, FoxO1 can promote the transcription of orexigenic neuropeptides (NPY/AgRP) in the hypothalamus, whereas insulin signaling is responsible for the disruption of this process. However, it is not understood if the hypothalamic activation of MKP-3 affects FoxO1 phosphorylation, and we hypothesized that MKP-3 overexpression reduces the capacity of the insulin signal to phosphorylate FoxO1. In the present study, we overexpressed the DUSP6 gene through an injection of adenovirus directly into the hypothalamic third ventricle of Swiss mice. The colocalization of the adenovirus was confirmed by the immunofluorescence assay. Then, MKP-3 overexpression resulted in a significant reduction of hypothalamic FoxO1 phosphorylation after insulin stimulation. This effect was independent of changes in Akt phosphorylation. Thus, the role of MKP-3 in the hypothalamus is closely associated with FoxO1 dephosphorylation and may provide a potential therapeutic target against hypothalamic disorders related to obesity and unbalanced food intake control.
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spelling Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice hypothalamusHypothalamusInsulinMKP-3The mitogen-activated kinase phosphatase-3 (MKP-3) has gained great importance in the scientific community by acting as a regulator of the cell cycle through dephosphorylation of FoxO1, an important transcription factor involved in the insulin intracellular signaling cascade. When dephosphorylated and translocated to the nuclei, FoxO1 can promote the transcription of orexigenic neuropeptides (NPY/AgRP) in the hypothalamus, whereas insulin signaling is responsible for the disruption of this process. However, it is not understood if the hypothalamic activation of MKP-3 affects FoxO1 phosphorylation, and we hypothesized that MKP-3 overexpression reduces the capacity of the insulin signal to phosphorylate FoxO1. In the present study, we overexpressed the DUSP6 gene through an injection of adenovirus directly into the hypothalamic third ventricle of Swiss mice. The colocalization of the adenovirus was confirmed by the immunofluorescence assay. Then, MKP-3 overexpression resulted in a significant reduction of hypothalamic FoxO1 phosphorylation after insulin stimulation. This effect was independent of changes in Akt phosphorylation. Thus, the role of MKP-3 in the hypothalamus is closely associated with FoxO1 dephosphorylation and may provide a potential therapeutic target against hypothalamic disorders related to obesity and unbalanced food intake control.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)School of Applied Sciences University of CampinasPost-Graduate Program in Movement Sciences São Paulo State University (Unesp) Institute of BiosciencesSchool of Physical Education and Sport of Ribeirao Preto University of Sao Paulo, Ribeirao PretoPost-Graduate Program in Movement Sciences São Paulo State University (Unesp) Institute of BiosciencesUniversidade Estadual de Campinas (UNICAMP)Universidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Rodrigues, Bárbara de AlmeidaKuga, Gabriel Keine [UNESP]Muñoz, Vitor RosettoGaspar, Rafael CalaisTavares, Mariana RosolenBotezelli, José Diegoda Silva, Adelino Sanchez RamosCintra, Dennys Esperde Moura, Leandro PereiraSimabuco, Fernando MoreiraRopelle, Eduardo RochetePauli, José Rodrigo2018-12-11T16:49:13Z2018-12-11T16:49:13Z2017-10-17info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article14-17application/pdfhttp://dx.doi.org/10.1016/j.neulet.2017.08.067Neuroscience Letters, v. 659, p. 14-17.1872-79720304-3940http://hdl.handle.net/11449/17009110.1016/j.neulet.2017.08.0672-s2.0-850286923842-s2.0-85028692384.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengNeuroscience Letters0,946info:eu-repo/semantics/openAccess2024-01-04T06:23:59Zoai:repositorio.unesp.br:11449/170091Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T22:05:15.094136Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice hypothalamus
title Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice hypothalamus
spellingShingle Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice hypothalamus
Rodrigues, Bárbara de Almeida
Hypothalamus
Insulin
MKP-3
title_short Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice hypothalamus
title_full Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice hypothalamus
title_fullStr Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice hypothalamus
title_full_unstemmed Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice hypothalamus
title_sort Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice hypothalamus
author Rodrigues, Bárbara de Almeida
author_facet Rodrigues, Bárbara de Almeida
Kuga, Gabriel Keine [UNESP]
Muñoz, Vitor Rosetto
Gaspar, Rafael Calais
Tavares, Mariana Rosolen
Botezelli, José Diego
da Silva, Adelino Sanchez Ramos
Cintra, Dennys Esper
de Moura, Leandro Pereira
Simabuco, Fernando Moreira
Ropelle, Eduardo Rochete
Pauli, José Rodrigo
author_role author
author2 Kuga, Gabriel Keine [UNESP]
Muñoz, Vitor Rosetto
Gaspar, Rafael Calais
Tavares, Mariana Rosolen
Botezelli, José Diego
da Silva, Adelino Sanchez Ramos
Cintra, Dennys Esper
de Moura, Leandro Pereira
Simabuco, Fernando Moreira
Ropelle, Eduardo Rochete
Pauli, José Rodrigo
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual de Campinas (UNICAMP)
Universidade Estadual Paulista (Unesp)
Universidade de São Paulo (USP)
dc.contributor.author.fl_str_mv Rodrigues, Bárbara de Almeida
Kuga, Gabriel Keine [UNESP]
Muñoz, Vitor Rosetto
Gaspar, Rafael Calais
Tavares, Mariana Rosolen
Botezelli, José Diego
da Silva, Adelino Sanchez Ramos
Cintra, Dennys Esper
de Moura, Leandro Pereira
Simabuco, Fernando Moreira
Ropelle, Eduardo Rochete
Pauli, José Rodrigo
dc.subject.por.fl_str_mv Hypothalamus
Insulin
MKP-3
topic Hypothalamus
Insulin
MKP-3
description The mitogen-activated kinase phosphatase-3 (MKP-3) has gained great importance in the scientific community by acting as a regulator of the cell cycle through dephosphorylation of FoxO1, an important transcription factor involved in the insulin intracellular signaling cascade. When dephosphorylated and translocated to the nuclei, FoxO1 can promote the transcription of orexigenic neuropeptides (NPY/AgRP) in the hypothalamus, whereas insulin signaling is responsible for the disruption of this process. However, it is not understood if the hypothalamic activation of MKP-3 affects FoxO1 phosphorylation, and we hypothesized that MKP-3 overexpression reduces the capacity of the insulin signal to phosphorylate FoxO1. In the present study, we overexpressed the DUSP6 gene through an injection of adenovirus directly into the hypothalamic third ventricle of Swiss mice. The colocalization of the adenovirus was confirmed by the immunofluorescence assay. Then, MKP-3 overexpression resulted in a significant reduction of hypothalamic FoxO1 phosphorylation after insulin stimulation. This effect was independent of changes in Akt phosphorylation. Thus, the role of MKP-3 in the hypothalamus is closely associated with FoxO1 dephosphorylation and may provide a potential therapeutic target against hypothalamic disorders related to obesity and unbalanced food intake control.
publishDate 2017
dc.date.none.fl_str_mv 2017-10-17
2018-12-11T16:49:13Z
2018-12-11T16:49:13Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.neulet.2017.08.067
Neuroscience Letters, v. 659, p. 14-17.
1872-7972
0304-3940
http://hdl.handle.net/11449/170091
10.1016/j.neulet.2017.08.067
2-s2.0-85028692384
2-s2.0-85028692384.pdf
url http://dx.doi.org/10.1016/j.neulet.2017.08.067
http://hdl.handle.net/11449/170091
identifier_str_mv Neuroscience Letters, v. 659, p. 14-17.
1872-7972
0304-3940
10.1016/j.neulet.2017.08.067
2-s2.0-85028692384
2-s2.0-85028692384.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Neuroscience Letters
0,946
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 14-17
application/pdf
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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