Artículo
RhoA and MAPKinase signal transduction pathways regulate NHE1 Na+/H+ exchanger-dependent proximal tubule cell apoptosis following mechanical stretch
Bocanegra, María Victoria
; Gil Lorenzo, Andrea Fernanda
; Cacciamani, Valeria
; Benardon, María Eugenia; Costantino, Valeria Victoria
; Vallés, Patricia G.
Fecha de publicación:
10/2014
Editorial:
American Physiological Society
Revista:
American Journal Of Physiology-renal Physiology
ISSN:
0363-6127
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
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Articulos(IMBECU)
Articulos de INST. DE MEDICINA Y BIO. EXP. DE CUYO
Articulos de INST. DE MEDICINA Y BIO. EXP. DE CUYO
Citación
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
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