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dc.contributor.author Gorostizaga, Alejandra Beatriz
dc.contributor.author Mori Sequeiros, María de Las Mercedes
dc.contributor.author Acquier, Andrea Beatriz
dc.contributor.author Gómez, Natalia
dc.contributor.author Maloberti, Paula Mariana
dc.contributor.author Mendez, Carlos Fernando
dc.contributor.author Paz, Cristina del Valle
dc.date.available 2017-04-12T18:52:21Z
dc.date.issued 2013-10
dc.identifier.citation Gorostizaga, Alejandra Beatriz; Mori Sequeiros, María de Las Mercedes; Acquier, Andrea Beatriz; Gómez, Natalia; Maloberti, Paula Mariana; et al.; Modulation of albumin-induced endoplasmic reticulum stress in renal proximal tubule cells by upregulation of mapk phosphatase-1; Elsevier Ireland; Chemico-biological Interactions; 206; 1; 10-2013; 47-54
dc.identifier.issn 0009-2797
dc.identifier.uri http://hdl.handle.net/11336/15224
dc.description.abstract High amounts of albumin in urine cause tubulointerstitial damage that leads to a rapid deterioration of the renal function. Albumin exerts its injurious effects on renal cells through a process named endoplasmic reticulum (ER) stress due to the accumulation of unfolded proteins in the ER lumen. In addition, albumin promotes phosphorylation and consequent activation of MAPKs such as ERK1/2. Since ERK1/2 activation promoted by albumin is a transient event, the aims of the present work were to identify the phosphatase involved in their dephosphorylation in albumin-exposed cells and to analyze the putative regulation of this phosphatase by albumin. We also sought to determine the role played by the phospho/dephosphorylation of ERK1/2 in the cellular response to albumin-induced ER stress. MAP kinase phosphatase-1, MKP-1, is a nuclear enzyme involved in rapid MAPK dephosphorylation. Here we present evidence supporting the notion that this phosphatase is responsible for ERK1/2 dephosphorylation after albumin exposure in OK cells. Moreover, we demonstrate that exposure of OK cells to albumin transiently increases MKP-1 protein levels. The increase was evident after 15 min of exposure, peaked at 1 h (6-fold) and declined thereafter. In cells overexpressing flag-MKP-1, albumin caused the accumulation of this chimera, promoting MKP-1 stabilization by a posttranslational mechanism. Albumin also promoted a transient increase in MKP-1 mRNA levels (3-fold at 1 h) through the activation of gene transcription. In addition, we also show that albumin increased mRNA levels of GRP78, a key marker of ER stress, through an ERK-dependent pathway. In line with this finding, our studies demonstrate that flag-MKP-1 overexpression blunted albumin-induced GRP78 upregulation. Thus, our work demonstrates that albumin overload not only triggers MAPK activation but also tightly upregulates MKP-1 expression, which might modulate ER stress response to albumin overload.
dc.format application/pdf
dc.language.iso eng
dc.publisher Elsevier Ireland
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject Albumin
dc.subject OK cells
dc.subject ERK1/2
dc.subject MKPs
dc.subject Endoplasmic reticulum stress
dc.subject.classification Bioquímica y Biología Molecular
dc.subject.classification Medicina Básica
dc.subject.classification CIENCIAS MÉDICAS Y DE LA SALUD
dc.title Modulation of albumin-induced endoplasmic reticulum stress in renal proximal tubule cells by upregulation of mapk phosphatase-1
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2017-04-07T14:28:04Z
dc.journal.volume 206
dc.journal.number 1
dc.journal.pagination 47-54
dc.journal.pais Irlanda
dc.journal.ciudad Shannon
dc.description.fil Fil: Gorostizaga, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina
dc.description.fil Fil: Mori Sequeiros, María de Las Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina
dc.description.fil Fil: Acquier, Andrea Beatriz. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina
dc.description.fil Fil: Gómez, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina
dc.description.fil Fil: Maloberti, Paula Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina
dc.description.fil Fil: Mendez, Carlos Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina
dc.description.fil Fil: Paz, Cristina del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina
dc.journal.title Chemico-biological Interactions
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S000927971300210X
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.cbi.2013.08.009


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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)