title: Activation of the mineralocorticoid receptor increases striatin levels.
abstract: BACKGROUND
  Aldosterone (ALDO), a critical regulator of sodium homeostasis, mediates its effects via activation of the mineralocorticoid receptor (MR) through mechanisms that are not entirely clear. Striatin, a membrane associated protein, interacts with estrogen receptors in endothelial cells.
  
  
  METHODS
  We studied the effects of MR activation in vitro and in vivo on striatin levels in vascular tissue.
  
  
  RESULTS
  We observed that dietary sodium restriction was associated with increased striatin levels in mouse heart and aorta and that striatin and MR are present in the human endothelial cell line, (EA.hy926), and in mouse aortic endothelial cells (MAEC). Further, we show that MR co-precipitates with striatin in vascular tissue. Incubation of EA.hy926 cells with ALDO (10(-8) mol/l for 5-24 h) increases striatin protein and mRNA expression, an effect that was inhibited by canrenoic acid, an MR antagonist. Consistent with these observations, incubation of MAEC with ALDO increased striatin levels that were likewise blocked by canrenoic acid. To test the in vivo relevance of these findings, we studied two previously described mouse models of increased ALDO levels. Intraperitoneal ALDO administration augmented the abundance of striatin protein in mouse heart. We also observed that in a murine model of chronic ALDO-mediated cardiovascular damage following treatment with N(G)-nitro-L-arginine methyl ester plus angiotensin II an increased abundance of striatin protein in heart and kidney tissue.
  
  
  CONCLUSIONS
  Our results provide evidence that increased striatin levels is a component of MR activation in the vasculature and suggest that regulation of striatin by ALDO may modulate estrogen's nongenomic effects.
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Luminita H
authors.initials: LH
authors.lastname: Pojoga
authors.forename: Patricia
authors.initials: P
authors.lastname: Coutinho
authors.forename: Alicia
authors.initials: A
authors.lastname: Rivera
authors.forename: Tham M
authors.initials: TM
authors.lastname: Yao
authors.forename: Enrique R
authors.initials: ER
authors.lastname: Maldonado
authors.forename: Rodeler
authors.initials: R
authors.lastname: Youte
authors.forename: Gail K
authors.initials: GK
authors.lastname: Adler
authors.forename: Jonathan
authors.initials: J
authors.lastname: Williams
authors.forename: Alexander
authors.initials: A
authors.lastname: Turchin
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Williams
authors.forename: Jose R
authors.initials: JR
authors.lastname: Romero
mesh_terms: D000450:Aldosterone / Q000008:administration & dosage / Q000502:physiology; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000096:biosynthesis*; D002191:Canrenoic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D004039:Diet, Sodium-Restricted; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*
chemical_list: D002148:Calmodulin-Binding Proteins; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D000451:Mineralocorticoid Receptor Antagonists; D009419:Nerve Tissue Proteins; D018161:Receptors, Mineralocorticoid; C491924:Strn protein, mouse; D000804:Angiotensin II; D000450:Aldosterone; D002191:Canrenoic Acid; D019331:NG-Nitroarginine Methyl Ester
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