Effects of aldosterone on striatin and caveolin-1 protein levels in rat kidney: role of mineralocorticoid receptor

Abstract

The mineralocorticoid hormone aldosterone is a steroid hormone which plays an important role in maintenance of sodium, potassium, and acid-base balance. Aldosterone actions are mediated by mineralocorticoid receptor (MR) that could operate via genomic or nongenomic pathways. It has been shown that MR forms a complex with several molecules including scaffolding proteins, such as striatin and caveolin-1 (cav-1). Previous in vitro studies demonstrated that aldosterone increased striatin and cav-1 protein abundance. In addition, both striatin and cav-1 could interact with MR. However, there is no in vivo study of aldosterone effects on striatin and cav-1 protein levels in rat kidney. Male Wistar rats were divided into two main groups: 30 minutes and 2 hours. Each main group further divided into 3 subgroups: sham (normal saline solution; ip), aldosterone (Aldo: 150 µg/kg BW) or eplerenone [mineralocorticoid receptor (MR) blocker, 15 mg/kg BW] 30 minutes before aldosterone injection. Thirty minutes or two hours after aldosterone administration, protein abundance and localization of striatin and cav-1 were determined by Western blot analysis and immunohistochemistry, respectively. In addition, the protein interaction of striatin/MR, cav-1/MR, and cav-1/striatin was measured by co-immunoprecipitation and Western blot analysis. The results from 30-minute group showed that aldosterone increased protein abundances of striatin and cav-1 to 150% (p<0.05) and 200% (p<0.001), respectively. Eplerenone had no significant effect on striatin levels, whereas cav-1 protein was partially blocked by eplerenone. For 2-hour group, protein abundances of striatin and cav-1 were remained after aldosterone injection. Interestingly, eplerenone pretreatment significantly suppressed cav-1 protein levels. Aldosterone stimulated striatin and cav-1 protein immunoreactivity in both cortex and medulla. Eplerenone minimized striatin and cav-1 immunostaining in the cortex. For protein interaction, the data showed that either striatin or cav-1 was able to interact with MR in rat kidney. This is the first in vivo study demonstrating that, in rat kidney, aldosterone differently modulates striatin and cav-1 protein levels. In a rapid action, aldosterone increases striatin via MR-independent manner, whereas it partially induces cav-1 through MR-dependent pathway. For a longer effect, aldosterone had no significant alterations on striatin and cav-1 protein levels. Blockage of MR could disturb aldosterone actions on cav-1 protein.