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dc.contributor.author
Bocanegra, María Victoria
dc.contributor.author
Gil Lorenzo, Andrea Fernanda
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Cacciamani, Valeria
dc.contributor.author
Benardon, María Eugenia
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Costantino, Valeria Victoria
dc.contributor.author
Vallés, Patricia G.
dc.date.available
2019-08-07T20:11:13Z
dc.date.issued
2014-10
dc.identifier.citation
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
dc.identifier.issn
0363-6127
dc.identifier.uri
http://hdl.handle.net/11336/81160
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Physiological Society
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Apoptosis
dc.subject
Mechanical Stretch
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Mitogen-Activated Protein Kinases
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Na+/H+ Exchanger 1
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Proximal Tubule Cell
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Rhoa
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Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
RhoA and MAPKinase signal transduction pathways regulate NHE1 Na+/H+ exchanger-dependent proximal tubule cell apoptosis following mechanical stretch
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-06-11T15:16:27Z
dc.journal.volume
307
dc.journal.number
7
dc.journal.pagination
F881-F889
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Bethesda
dc.description.fil
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
dc.description.fil
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
dc.description.fil
Fil: Cacciamani, Valeria. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
dc.description.fil
Fil: Benardon, María Eugenia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina
dc.description.fil
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
dc.description.fil
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
dc.journal.title
American Journal Of Physiology-renal Physiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1152/ajprenal.00232.2014
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/full/10.1152/ajprenal.00232.2014
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