title: Rapid mineralocorticoid receptor trafficking.
abstract: The mineralocorticoid receptor (MR) is a ligand-dependent transcription factor that physiologically regulates water-electrolyte homeostasis and controls blood pressure. The MR can also elicit inflammatory and remodeling processes in the cardiovascular system and the kidneys, which require the presence of additional pathological factors like for example nitrosative stress. However, the underlying molecular mechanism(s) for pathophysiological MR effects remain(s) elusive. The inactive MR is located in the cytosol associated with chaperone molecules including HSP90. After ligand binding, the MR monomer rapidly translocates into the nucleus while still being associated to HSP90 and after dissociation from HSP90 binds to hormone-response-elements called glucocorticoid response elements (GREs) as a dimer. There are indications that rapid MR trafficking is modulated in the presence of high salt, oxidative or nitrosative stress, hypothetically by induction or posttranslational modifications. Additionally, glucocorticoids and the enzyme 11beta hydroxysteroid dehydrogenase may also influence MR activation. Because MR trafficking and its modulation by micro-milieu factors influence MR cellular localization, it is not only relevant for genomic but also for nongenomic MR effects.
authors.affiliation: Julius Bernstein Institute of Physiology, Martin Luther University Halle-Wittenberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gekle
authors.affiliation: Julius Bernstein Institute of Physiology, Martin Luther University Halle-Wittenberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bretschneider
authors.affiliation: Julius Bernstein Institute of Physiology, Martin Luther University Halle-Wittenberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Meinel
authors.affiliation: Julius Bernstein Institute of Physiology, Martin Luther University Halle-Wittenberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ruhs
authors.affiliation: Julius Bernstein Institute of Physiology, Martin Luther University Halle-Wittenberg, Germany. Electronic address: claudia.grossmann@medizin.uni-halle.de.
authors.forename: C
authors.initials: C
authors.lastname: Grossmann
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress; D021381:Protein Transport; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements
chemical_list: D018841:HSP90 Heat-Shock Proteins; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone
keywords: Genomic signaling; Mineralocorticoid receptor; Modulation; Trafficking