RhoA and MAPKinase signal transduction pathways regulate NHE1 Na+/H+ exchanger-dependent proximal tubule cell apoptosis following mechanical stretch

Autores
Bocanegra, María Victoria; Gil Lorenzo, Andrea Fernanda; Cacciamani, Valeria; Benardon, María Eugenia; Costantino, Valeria Victoria; Vallés, Patricia G.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mechanical deformation after congenital ureteral obstruction is traduced into biochemical signals leading to tubular atrophy due to epithelial cell apoptosis. We investigated whether Na+/H+ exchanger 1 (NHE1) could be responsible for HK-2 cell apoptosis induction in response to mechanical stretch through its ability to function as a control point of RhoA and MAPK signaling pathways. When mechanical stretch was applied to HK-2 cells, cell apoptosis was associated with diminished NHE1 expression and RhoA activation. The RhoA signaling pathway was confirmed to be upstream from the MAPK cascade when HK-2 cells were transfected with the active RhoA-V14 mutant, showing higher ERK1/2 expression and decreased p38 activation associated with NHE1 downregulation. NHE1 participation in apoptosis induction was confirmed by specific small interfering RNA NHE1 showing caspase-3 activation and decreased Bcl-2 expression. The decreased NHE1 expression was correlated with abnormal NHE1 activity addressed by intracellular pH measurements. These results demonstrate that mitochondrial proximal tubule cell apoptosis in response to mechanical stretch is orchestrated by signaling pathways initiated by the small GTPase RhoA and followed by the opposing effects of ERK1/2 and p38 MAPK phosphorylation, regulating NHE1 decreased expression and activity.
Fil: Bocanegra, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Gil Lorenzo, Andrea Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Cacciamani, Valeria. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Benardon, María Eugenia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Costantino, Valeria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Vallés, Patricia G.. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Materia
Apoptosis
Mechanical Stretch
Mitogen-Activated Protein Kinases
Na+/H+ Exchanger 1
Proximal Tubule Cell
Rhoa
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/81160
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/81160
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling RhoA and MAPKinase signal transduction pathways regulate NHE1 Na+/H+ exchanger-dependent proximal tubule cell apoptosis following mechanical stretchBocanegra, María VictoriaGil Lorenzo, Andrea FernandaCacciamani, ValeriaBenardon, María EugeniaCostantino, Valeria VictoriaVallés, Patricia G.ApoptosisMechanical StretchMitogen-Activated Protein KinasesNa+/H+ Exchanger 1Proximal Tubule CellRhoahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Mechanical deformation after congenital ureteral obstruction is traduced into biochemical signals leading to tubular atrophy due to epithelial cell apoptosis. We investigated whether Na+/H+ exchanger 1 (NHE1) could be responsible for HK-2 cell apoptosis induction in response to mechanical stretch through its ability to function as a control point of RhoA and MAPK signaling pathways. When mechanical stretch was applied to HK-2 cells, cell apoptosis was associated with diminished NHE1 expression and RhoA activation. The RhoA signaling pathway was confirmed to be upstream from the MAPK cascade when HK-2 cells were transfected with the active RhoA-V14 mutant, showing higher ERK1/2 expression and decreased p38 activation associated with NHE1 downregulation. NHE1 participation in apoptosis induction was confirmed by specific small interfering RNA NHE1 showing caspase-3 activation and decreased Bcl-2 expression. The decreased NHE1 expression was correlated with abnormal NHE1 activity addressed by intracellular pH measurements. These results demonstrate that mitochondrial proximal tubule cell apoptosis in response to mechanical stretch is orchestrated by signaling pathways initiated by the small GTPase RhoA and followed by the opposing effects of ERK1/2 and p38 MAPK phosphorylation, regulating NHE1 decreased expression and activity.Fil: Bocanegra, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Gil Lorenzo, Andrea Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Cacciamani, Valeria. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Benardon, María Eugenia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Costantino, Valeria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Vallés, Patricia G.. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaAmerican Physiological Society2014-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/81160Bocanegra, María Victoria; Gil Lorenzo, Andrea Fernanda; Cacciamani, Valeria; Benardon, María Eugenia; Costantino, Valeria Victoria; et al.; RhoA and MAPKinase signal transduction pathways regulate NHE1 Na+/H+ exchanger-dependent proximal tubule cell apoptosis following mechanical stretch; American Physiological Society; American Journal Of Physiology-renal Physiology; 307; 7; 10-2014; F881-F8890363-6127CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1152/ajprenal.00232.2014info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/full/10.1152/ajprenal.00232.2014info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:44Zoai:ri.conicet.gov.ar:11336/81160instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:59:44.562CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv RhoA and MAPKinase signal transduction pathways regulate NHE1 Na+/H+ exchanger-dependent proximal tubule cell apoptosis following mechanical stretch
title RhoA and MAPKinase signal transduction pathways regulate NHE1 Na+/H+ exchanger-dependent proximal tubule cell apoptosis following mechanical stretch
spellingShingle RhoA and MAPKinase signal transduction pathways regulate NHE1 Na+/H+ exchanger-dependent proximal tubule cell apoptosis following mechanical stretch
Bocanegra, María Victoria
Apoptosis
Mechanical Stretch
Mitogen-Activated Protein Kinases
Na+/H+ Exchanger 1
Proximal Tubule Cell
Rhoa
title_short RhoA and MAPKinase signal transduction pathways regulate NHE1 Na+/H+ exchanger-dependent proximal tubule cell apoptosis following mechanical stretch
title_full RhoA and MAPKinase signal transduction pathways regulate NHE1 Na+/H+ exchanger-dependent proximal tubule cell apoptosis following mechanical stretch
title_fullStr RhoA and MAPKinase signal transduction pathways regulate NHE1 Na+/H+ exchanger-dependent proximal tubule cell apoptosis following mechanical stretch
title_full_unstemmed RhoA and MAPKinase signal transduction pathways regulate NHE1 Na+/H+ exchanger-dependent proximal tubule cell apoptosis following mechanical stretch
title_sort RhoA and MAPKinase signal transduction pathways regulate NHE1 Na+/H+ exchanger-dependent proximal tubule cell apoptosis following mechanical stretch
dc.creator.none.fl_str_mv Bocanegra, María Victoria
Gil Lorenzo, Andrea Fernanda
Cacciamani, Valeria
Benardon, María Eugenia
Costantino, Valeria Victoria
Vallés, Patricia G.
author Bocanegra, María Victoria
author_facet Bocanegra, María Victoria
Gil Lorenzo, Andrea Fernanda
Cacciamani, Valeria
Benardon, María Eugenia
Costantino, Valeria Victoria
Vallés, Patricia G.
author_role author
author2 Gil Lorenzo, Andrea Fernanda
Cacciamani, Valeria
Benardon, María Eugenia
Costantino, Valeria Victoria
Vallés, Patricia G.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Apoptosis
Mechanical Stretch
Mitogen-Activated Protein Kinases
Na+/H+ Exchanger 1
Proximal Tubule Cell
Rhoa
topic Apoptosis
Mechanical Stretch
Mitogen-Activated Protein Kinases
Na+/H+ Exchanger 1
Proximal Tubule Cell
Rhoa
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Mechanical deformation after congenital ureteral obstruction is traduced into biochemical signals leading to tubular atrophy due to epithelial cell apoptosis. We investigated whether Na+/H+ exchanger 1 (NHE1) could be responsible for HK-2 cell apoptosis induction in response to mechanical stretch through its ability to function as a control point of RhoA and MAPK signaling pathways. When mechanical stretch was applied to HK-2 cells, cell apoptosis was associated with diminished NHE1 expression and RhoA activation. The RhoA signaling pathway was confirmed to be upstream from the MAPK cascade when HK-2 cells were transfected with the active RhoA-V14 mutant, showing higher ERK1/2 expression and decreased p38 activation associated with NHE1 downregulation. NHE1 participation in apoptosis induction was confirmed by specific small interfering RNA NHE1 showing caspase-3 activation and decreased Bcl-2 expression. The decreased NHE1 expression was correlated with abnormal NHE1 activity addressed by intracellular pH measurements. These results demonstrate that mitochondrial proximal tubule cell apoptosis in response to mechanical stretch is orchestrated by signaling pathways initiated by the small GTPase RhoA and followed by the opposing effects of ERK1/2 and p38 MAPK phosphorylation, regulating NHE1 decreased expression and activity.
Fil: Bocanegra, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Gil Lorenzo, Andrea Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Cacciamani, Valeria. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Benardon, María Eugenia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
Fil: Costantino, Valeria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Vallés, Patricia G.. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
description Mechanical deformation after congenital ureteral obstruction is traduced into biochemical signals leading to tubular atrophy due to epithelial cell apoptosis. We investigated whether Na+/H+ exchanger 1 (NHE1) could be responsible for HK-2 cell apoptosis induction in response to mechanical stretch through its ability to function as a control point of RhoA and MAPK signaling pathways. When mechanical stretch was applied to HK-2 cells, cell apoptosis was associated with diminished NHE1 expression and RhoA activation. The RhoA signaling pathway was confirmed to be upstream from the MAPK cascade when HK-2 cells were transfected with the active RhoA-V14 mutant, showing higher ERK1/2 expression and decreased p38 activation associated with NHE1 downregulation. NHE1 participation in apoptosis induction was confirmed by specific small interfering RNA NHE1 showing caspase-3 activation and decreased Bcl-2 expression. The decreased NHE1 expression was correlated with abnormal NHE1 activity addressed by intracellular pH measurements. These results demonstrate that mitochondrial proximal tubule cell apoptosis in response to mechanical stretch is orchestrated by signaling pathways initiated by the small GTPase RhoA and followed by the opposing effects of ERK1/2 and p38 MAPK phosphorylation, regulating NHE1 decreased expression and activity.
publishDate 2014
dc.date.none.fl_str_mv 2014-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/81160
Bocanegra, María Victoria; Gil Lorenzo, Andrea Fernanda; Cacciamani, Valeria; Benardon, María Eugenia; Costantino, Valeria Victoria; et al.; RhoA and MAPKinase signal transduction pathways regulate NHE1 Na+/H+ exchanger-dependent proximal tubule cell apoptosis following mechanical stretch; American Physiological Society; American Journal Of Physiology-renal Physiology; 307; 7; 10-2014; F881-F889
0363-6127
CONICET Digital
CONICET
url http://hdl.handle.net/11336/81160
identifier_str_mv Bocanegra, María Victoria; Gil Lorenzo, Andrea Fernanda; Cacciamani, Valeria; Benardon, María Eugenia; Costantino, Valeria Victoria; et al.; RhoA and MAPKinase signal transduction pathways regulate NHE1 Na+/H+ exchanger-dependent proximal tubule cell apoptosis following mechanical stretch; American Physiological Society; American Journal Of Physiology-renal Physiology; 307; 7; 10-2014; F881-F889
0363-6127
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1152/ajprenal.00232.2014
info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/full/10.1152/ajprenal.00232.2014
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269598671437824
score 13.13397

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