MKP-1 mediates glucocorticoid-induced ERK1/2 dephosphorylation and reduction in pancreatic beta-cell proliferation in islets from early lactating mothers

Detalhes bibliográficos
Autor(a) principal: Nicoletti-Carvalho, Jose E.
Data de Publicação: 2010
Outros Autores: Lellis-Santos, Camilo, Yamanaka, Tatiana S., Nogueira, Tatiane C., Caperuto, Luciana C. [UNIFESP], Leite, Adriana R., Anhe, Gabriel F., Bordin, Silvana
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://dx.doi.org/10.1152/ajpendo.00341.2010
http://repositorio.unifesp.br/handle/11600/33094
Resumo: Maternal pancreatic islets undergo a robust increase of mass and proliferation during pregnancy, which allows a compensation of gestational insulin resistance. Studies have described that this adaptation switches to a low proliferative status after the delivery. the mechanisms underlying this reversal are unknown, but the action of glucocorticoids (GCs) is believed to play an important role because GCs counteract the pregnancy-like effects of PRL on isolated pancreatic islets maintained in cell culture. Here, we demonstrate that ERK1/2 phosphorylation (phospho-ERK1/2) is increased in maternal rat islets isolated on the 19th day of pregnancy. Phospho-ERK1/2 status on the 3rd day after delivery (L3) rapidly turns to values lower than that found in virgin control rats (CTL). MKP-1, a protein phosphatase able to dephosphorylate ERK1/2, is increased in islets from L3 rats. Chromatin immunoprecipitation assay revealed that binding of glucocorticoid receptor (GR) to MKP-1 promoter is also increased in islets from L3 rats. in addition, dexamethasone (DEX) reduced phospho-ERK1/2 and increased MKP-1 expression in RINm5F and MIN-6 cells. Inhibition of transduction with cycloheximide and inhibition of phosphatases with orthovanadate efficiently blocked DEX-induced downregulation of phospho-ERK1/2. in addition, specific knockdown of MKP-1 with siRNA suppressed the downregulation of phosphoERK1/2 and the reduction of proliferation induced by DEX. Altogether, our results indicate that downregulation of phospho-ERK1/2 is associated with reduction in proliferation found in islets of early lactating mothers. This mechanism is probably mediated by GC-induced MKP-1 expression.
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spelling MKP-1 mediates glucocorticoid-induced ERK1/2 dephosphorylation and reduction in pancreatic beta-cell proliferation in islets from early lactating mothersmitogen-activated protein kinase phosphatase-1extracellular signal-regulated kinase 1/2dual-specificity phosphatasespregnancylactationMaternal pancreatic islets undergo a robust increase of mass and proliferation during pregnancy, which allows a compensation of gestational insulin resistance. Studies have described that this adaptation switches to a low proliferative status after the delivery. the mechanisms underlying this reversal are unknown, but the action of glucocorticoids (GCs) is believed to play an important role because GCs counteract the pregnancy-like effects of PRL on isolated pancreatic islets maintained in cell culture. Here, we demonstrate that ERK1/2 phosphorylation (phospho-ERK1/2) is increased in maternal rat islets isolated on the 19th day of pregnancy. Phospho-ERK1/2 status on the 3rd day after delivery (L3) rapidly turns to values lower than that found in virgin control rats (CTL). MKP-1, a protein phosphatase able to dephosphorylate ERK1/2, is increased in islets from L3 rats. Chromatin immunoprecipitation assay revealed that binding of glucocorticoid receptor (GR) to MKP-1 promoter is also increased in islets from L3 rats. in addition, dexamethasone (DEX) reduced phospho-ERK1/2 and increased MKP-1 expression in RINm5F and MIN-6 cells. Inhibition of transduction with cycloheximide and inhibition of phosphatases with orthovanadate efficiently blocked DEX-induced downregulation of phospho-ERK1/2. in addition, specific knockdown of MKP-1 with siRNA suppressed the downregulation of phosphoERK1/2 and the reduction of proliferation induced by DEX. Altogether, our results indicate that downregulation of phospho-ERK1/2 is associated with reduction in proliferation found in islets of early lactating mothers. This mechanism is probably mediated by GC-induced MKP-1 expression.Univ São Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, Diadema, SP, BrazilUniv Estadual Campinas, Fac Med Sci, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, Diadema, SP, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de PesquisaCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Amer Physiological SocUniversidade de São Paulo (USP)Universidade Federal de São Paulo (UNIFESP)Universidade Estadual de Campinas (UNICAMP)Nicoletti-Carvalho, Jose E.Lellis-Santos, CamiloYamanaka, Tatiana S.Nogueira, Tatiane C.Caperuto, Luciana C. [UNIFESP]Leite, Adriana R.Anhe, Gabriel F.Bordin, Silvana2016-01-24T14:05:42Z2016-01-24T14:05:42Z2010-12-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionE1006-E1015http://dx.doi.org/10.1152/ajpendo.00341.2010American Journal of Physiology-endocrinology and Metabolism. Bethesda: Amer Physiological Soc, v. 299, n. 6, p. E1006-E1015, 2010.10.1152/ajpendo.00341.20100193-1849http://repositorio.unifesp.br/handle/11600/33094WOS:000285710400017engAmerican Journal of Physiology-endocrinology and Metabolisminfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2022-02-18T12:08:03Zoai:repositorio.unifesp.br/:11600/33094Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652022-02-18T12:08:03Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv MKP-1 mediates glucocorticoid-induced ERK1/2 dephosphorylation and reduction in pancreatic beta-cell proliferation in islets from early lactating mothers
title MKP-1 mediates glucocorticoid-induced ERK1/2 dephosphorylation and reduction in pancreatic beta-cell proliferation in islets from early lactating mothers
spellingShingle MKP-1 mediates glucocorticoid-induced ERK1/2 dephosphorylation and reduction in pancreatic beta-cell proliferation in islets from early lactating mothers
Nicoletti-Carvalho, Jose E.
mitogen-activated protein kinase phosphatase-1
extracellular signal-regulated kinase 1/2
dual-specificity phosphatases
pregnancy
lactation
title_short MKP-1 mediates glucocorticoid-induced ERK1/2 dephosphorylation and reduction in pancreatic beta-cell proliferation in islets from early lactating mothers
title_full MKP-1 mediates glucocorticoid-induced ERK1/2 dephosphorylation and reduction in pancreatic beta-cell proliferation in islets from early lactating mothers
title_fullStr MKP-1 mediates glucocorticoid-induced ERK1/2 dephosphorylation and reduction in pancreatic beta-cell proliferation in islets from early lactating mothers
title_full_unstemmed MKP-1 mediates glucocorticoid-induced ERK1/2 dephosphorylation and reduction in pancreatic beta-cell proliferation in islets from early lactating mothers
title_sort MKP-1 mediates glucocorticoid-induced ERK1/2 dephosphorylation and reduction in pancreatic beta-cell proliferation in islets from early lactating mothers
author Nicoletti-Carvalho, Jose E.
author_facet Nicoletti-Carvalho, Jose E.
Lellis-Santos, Camilo
Yamanaka, Tatiana S.
Nogueira, Tatiane C.
Caperuto, Luciana C. [UNIFESP]
Leite, Adriana R.
Anhe, Gabriel F.
Bordin, Silvana
author_role author
author2 Lellis-Santos, Camilo
Yamanaka, Tatiana S.
Nogueira, Tatiane C.
Caperuto, Luciana C. [UNIFESP]
Leite, Adriana R.
Anhe, Gabriel F.
Bordin, Silvana
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Universidade Estadual de Campinas (UNICAMP)
dc.contributor.author.fl_str_mv Nicoletti-Carvalho, Jose E.
Lellis-Santos, Camilo
Yamanaka, Tatiana S.
Nogueira, Tatiane C.
Caperuto, Luciana C. [UNIFESP]
Leite, Adriana R.
Anhe, Gabriel F.
Bordin, Silvana
dc.subject.por.fl_str_mv mitogen-activated protein kinase phosphatase-1
extracellular signal-regulated kinase 1/2
dual-specificity phosphatases
pregnancy
lactation
topic mitogen-activated protein kinase phosphatase-1
extracellular signal-regulated kinase 1/2
dual-specificity phosphatases
pregnancy
lactation
description Maternal pancreatic islets undergo a robust increase of mass and proliferation during pregnancy, which allows a compensation of gestational insulin resistance. Studies have described that this adaptation switches to a low proliferative status after the delivery. the mechanisms underlying this reversal are unknown, but the action of glucocorticoids (GCs) is believed to play an important role because GCs counteract the pregnancy-like effects of PRL on isolated pancreatic islets maintained in cell culture. Here, we demonstrate that ERK1/2 phosphorylation (phospho-ERK1/2) is increased in maternal rat islets isolated on the 19th day of pregnancy. Phospho-ERK1/2 status on the 3rd day after delivery (L3) rapidly turns to values lower than that found in virgin control rats (CTL). MKP-1, a protein phosphatase able to dephosphorylate ERK1/2, is increased in islets from L3 rats. Chromatin immunoprecipitation assay revealed that binding of glucocorticoid receptor (GR) to MKP-1 promoter is also increased in islets from L3 rats. in addition, dexamethasone (DEX) reduced phospho-ERK1/2 and increased MKP-1 expression in RINm5F and MIN-6 cells. Inhibition of transduction with cycloheximide and inhibition of phosphatases with orthovanadate efficiently blocked DEX-induced downregulation of phospho-ERK1/2. in addition, specific knockdown of MKP-1 with siRNA suppressed the downregulation of phosphoERK1/2 and the reduction of proliferation induced by DEX. Altogether, our results indicate that downregulation of phospho-ERK1/2 is associated with reduction in proliferation found in islets of early lactating mothers. This mechanism is probably mediated by GC-induced MKP-1 expression.
publishDate 2010
dc.date.none.fl_str_mv 2010-12-01
2016-01-24T14:05:42Z
2016-01-24T14:05:42Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1152/ajpendo.00341.2010
American Journal of Physiology-endocrinology and Metabolism. Bethesda: Amer Physiological Soc, v. 299, n. 6, p. E1006-E1015, 2010.
10.1152/ajpendo.00341.2010
0193-1849
http://repositorio.unifesp.br/handle/11600/33094
WOS:000285710400017
url http://dx.doi.org/10.1152/ajpendo.00341.2010
http://repositorio.unifesp.br/handle/11600/33094
identifier_str_mv American Journal of Physiology-endocrinology and Metabolism. Bethesda: Amer Physiological Soc, v. 299, n. 6, p. E1006-E1015, 2010.
10.1152/ajpendo.00341.2010
0193-1849
WOS:000285710400017
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv American Journal of Physiology-endocrinology and Metabolism
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv E1006-E1015
dc.publisher.none.fl_str_mv Amer Physiological Soc
publisher.none.fl_str_mv Amer Physiological Soc
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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