INVESTIGADORES
RINALDI TOSI Martin Edgardo
artículos
Título:
Angiotensin AT1 Receptor Inhibition- Induced Apoptosis by RhoA GTPase activation and pERK1/2 signaling pathways in neonatal obstructive nephropathy
Autor/es:
BOCANEGRA V; RINALDI TOSI M; GIL LORENZO A; CACCIAMANI V; MANUCHA W; FORNES M; VALLES P
Revista:
HISTOLOGY AND HISTOPATHOLOGY
Editorial:
NIF
Referencias:
Lugar: Murcia; Año: 2011
ISSN:
0213-3911
Resumen:
Intrarenal renin- Angiotensin system (RAS) activity is increased during earlydevelopment and is further enhanced by unilateral ureteral obstruction (UUO).We studied the involvement of mitogen-activated protein (MAP) kinase members andthe RhoA GTPase signaling pathways on the regulation of renal cell response after AT1Angiotensin II receptor inhibition in obstruction.Neonatal rats subjected to sham operation or complete UUO within the first 48 hours oflife received saline vehicle, Losartan (AT1 inhibitor), or PD-123319 (AT2 inhibitor)during the first 14 days of life. Cortex tubular epithelial cell apoptotic response wasshown by TUNEL and confirmed by electron microscopy associated with mitochondrialsignaling pathway through the increased proapoptotic ratio Bax/BcL-2, andconsequently increased caspase 3 expression and activity in obstructed kidney beforeand after Type 1 (AT1) receptor blockade. Non injury of contralateral kidney was shown.The convergence of two independent signal pathways, the RhoA GTPase and pERK andconcurrent inhibition of JNK MAP kinase, were required for the apoptotic response in14 day kidney obstructed tubular cells either with or without Losartan treatment.Absence of increased AT2 protein expression after AT1 receptor inhibition on day 14 ofobstruction was shown. Selective AngiotensinAT2-receptor inhibition with PD-123319had no protective effect on the renal response to complete 14 day UUO.We suggest a role of both RhoA GTPase activation and the opposing actions of the ERKand JNK-MAP kinase signaling pathways as events involved in tubular cell apoptosisregulation in neonatal UUO. The selective AT1-receptor inhibition had no effect on therenal cellular response in the kidney subjected to UUO for 14 days.
