MKP-1 mediates glucocorticoid-induced ERK1/2 dephosphorylation and reduction in pancreatic beta-cell proliferation in islets from early lactating mothers
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , , , , , , |
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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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 |
_version_ |
1814268271154692096 |