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Rapid and Long Term Aldosterone Effect on the EGFR and ERK1/2 Phosphorylation in Rat Kidney ( in vivo )
Author(s) -
Pandolfi Kelly,
Szriber Shirley,
LeiteDellova Deise,
MelloAires Margarida
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.812.5
Subject(s) - endocrinology , medicine , kidney , phosphorylation , mineralocorticoid receptor , spironolactone , aldosterone , kinase , transactivation , renal cortex , chemistry , biology , transcription factor , biochemistry , gene
It's great the interest in the aldosterone (Aldo) mechanism of action, responsible for modulation of renal ionic transport, but also implicated in the kidney remodeling. Several mechanisms have been proposed for the pathological action of Aldo, including the transactivation of the epidermal growth factor receptor (EGFR) and the extracellular signal regulated kinases (ERK1/2) phosphorylation; however, the link between the rapid activation of these proteins and the development of renal injury is not completely understood. The objective of this study was to detect the EGFR and ERK1/2 phosphorylation in the cortex and medulla of rat kidney (Wistar, males, 320 g), by Western blot, after 30 min or 21 days of treatment with: control, Aldo (150 μg/Kg) and/or spironolactone (80 mg/Kg/30 min or 20 mg/Kg/21 days, MR receptor antagonist) or RU 486 (1 mg/Kg; a GR receptor antagonist). After 30 min, Aldo increased the EGFR and ERK1/2 phosphorylation in cortex (at 74% and 73%, respectively) and medulla (at 66% and 63%, respectively) over the control, and these effects were abolish by spironolactone and RU 486 (N=4, p<0.05). After 21 days, the treatments did not alter EGFR and ERK1/2 phosphorylation in both renal regions. These results suggest that both, EGFR and ERK1/2, participate of rapid Aldo mechanism in the kidney and the involvement of MR and GR in this process. Apparently, the hormonal effect was not maintained after 21 days. Aldo may induce proliferative and fibrotic responses in renal tissue; however, these effects may not be dependent of EGFR and ERK1/2 in the long term, like observed in cardiovascular system.