Expressions of EGFR-ERK 1/2-c-Src signaling mediators in a nongenomic pathway after aldosterone administration in rat kidney

Abstract

Aldosterone is the major mineralocorticoid hormone which plays an important role in maintenance of body sodium, potassium and acid-base balance. Many in vitro studies have demonstrated that aldosterone could enhance protein levels of phosphorylated epidermal growth factor receptor (pEGFR), and extracellular signal-related kinases 1/2 (pERK1/2) via nongenomic pathway. One of inter-mediators involved is phophorylated cytosolic tyrosine kinase of Src (pc-Src). However, there is no in vivo study of the protein abundances and expressions of pEGFR-pERK1/2-pc-Src signaling mediators through a nongenomic pathway in rat kidney. Male Wistar rats were received either normal saline solution (NSS) or aldosterone by intraperitoneal injection for 30 minutes. For aldosterone groupe, the rats were futher divided into two groups: low dose aldosterone (LA: 150 µg/kg BW) or high dose aldosterone (HA: 500 µg/kg BW). Protein abundance and localization of renal pEGFR, pERK1/2, and pc-Src were determined by Western blot and immunohistochemistry, respectively. After 30 minute of aldosterone injection, plasma aldosterone levels were markedly increased in both LA and HA groups (p<0.001). Aldosterone enhanced renal pEGFR and pERK1/2 protein abundances (p<0.001) but did not change in ps-Src prtein level. LA augmented pEGFR protein expression in the inner stripe of outer medulla and in the inner medulla regions while HA stimulated the expression in both cortex and medulla. Aldosterone elevated pERK1/2 protein expression in all studied areas. The cortical expression of cp-Src protein was increased by aldosterone with the redistribution of staining from the luminal membrane in the LA group to be the basolateral membrane in the HA group. However, both LA and HA activated renal pc-Src protein expression in the cortex but HA decreased the expression in the inner medulla area. These data first demonstrated that aldosterone, via nongenomic pathway, could elevate pEGFR and pERK 1/2 protein abundances and expressions in rat kidney. Aldosterone seems not to influence the total renal pc-Src protein abundance meanwhile the protein localization was obviously modulated.