title: Mineralocorticoid receptor is involved in the aldosterone pathway in human red blood cells.
abstract: We have recently demonstrated that excessive aldosterone (Aldo) secretion in primary aldosteronism (PA) is associated with red blood cells (RBC) senescence. These alterations were prevented/inhibited by cortisol (Cort) or canrenone (Can) raising the hypothesis that Aldo effects in RBC may be mediated by mineralocorticoid receptor (MR), though to date MR has never been demonstrated in human RBC. The aim of this multicenter comparative study was to investigate whether Aldo effects were mediated by MR in these a-nucleated cells. We included 12 healthy controls (HC) and 22 patients with PA. MR presence and activation were evaluated in RBC cytosol by glycerol gradient sedimentation, Western blotting, immuno-precipitation and radioimmunoassay. We demonstrated that RBC contained cytosolic MR, aggregated with HSP90 and other proteins to form multiprotein complex. Aldo induced MR to release from the complex and to form MR dimers which were quickly proteolyzed. Cort induced MR release but not dimers formation while Can was not able to induce MR release. In addition, RBC cytosol from PA patients contained significantly higher amounts of both MR fragments (p<0.0001) and Aldo (p<0.0001) concentrations. In conclusion, in RBC a genomic-like Aldo pathway is proposed involving MR activation, dimerization and proteolysis, but lacking nuclear transcription. In addition, dimers proteolysis may ensure a sort of Aldo scavenging from circulation by entrapping Aldo in MR fragments.
authors.affiliation: Department of Molecular Medicine-Biological Chemistry, University of Padua Padua, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Bordin
authors.affiliation: Department of Woman and Child Health, University of Padua Padua, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Saccardi
authors.affiliation: Department of Molecular Medicine-Biological Chemistry, University of Padua Padua, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Donà
authors.affiliation: Department of Medicine, University of Padua Padua, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sabbadin
authors.affiliation: Department of Woman and Child Health, University of Padua Padua, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Andrisani
authors.affiliation: Department of Woman and Child Health, University of Padua Padua, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Ambrosini
authors.affiliation: Department of Laboratory Medicine, University of Padua Padua, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.affiliation: Department of Molecular Medicine-Biological Chemistry, University of Padua Padua, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Brunati
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, University of Padua Padua, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Ragazzi
authors.affiliation: Department of Woman and Child Health, University of Padua Padua, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gizzo
authors.affiliation: Department of Medicine, University of Padua Padua, Italy.
authors.forename: Decio
authors.initials: D
authors.lastname: Armanini
keywords: HSP-90; Mineralocorticoid receptor; cellular senescence; cortisol; human red blood cells; primary aldosteronism