title: Induction of FKBP51 by aldosterone in intestinal epithelium.
abstract: Screening female rat distal colon preparations for aldosterone-induced genes identified the Hsp90-binding immunophilin FKBP51 as a major aldosterone-induced mRNA and protein. Limited induction of FKBP51 was observed also in other aldosterone-responsive tissues such as kidney medulla and heart. Ex vivo measurements in colonic tissue have characterized time course, dose response and receptor specificity of the induction of FKBP51. FKBP51 mRNA and protein were strongly up regulated by physiological concentrations of aldosterone in a late (greater than 2.5h) response to the hormone. Maximal increase in FKBP51 mRNA requires aldosterone concentrations that are higher than those needed to fully occupy the mineralocorticoid receptor (MR). Yet, the response is fully inhibited by the MR antagonist spironolactone and not inhibited and even stimulated by the glucocorticoid receptor (GR) antagonist RU486. These and related findings cannot be explained by a simple activation and dimerization of either MR or GR but are in agreement with response mediated by an MR-GR heterodimer. Overexpression or silencing FKBP51 in the kidney collecting duct cell line M1 had little or no effect on the aldosterone-induced increase in transepithelial Na(+) transport.
authors.affiliation: Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Petrovich
authors.forename: Carol
authors.initials: C
authors.lastname: Asher
authors.forename: Haim
authors.initials: H
authors.lastname: Garty
mesh_terms: D021581:Active Transport, Cell Nucleus; D000450:Aldosterone / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology / Q000378:metabolism; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005260:Female; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D019751:Intramolecular Transferases / Q000235:genetics / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000166:cytology; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D008901:Mineralocorticoids / Q000494:pharmacology / Q000502:physiology; D055550:Protein Stability; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000235:genetics* / Q000378:metabolism; D046509:Tissue Culture Techniques; D015533:Transcriptional Activation; D000099159:Tacrolimus Binding Protein 5
chemical_list: D000450:Aldosterone; D029681:Arabidopsis Proteins; D019751:Intramolecular Transferases; D015735:Mifepristone; D000451:Mineralocorticoid Receptor Antagonists; D008901:Mineralocorticoids; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C568454:marneral synthase, Arabidopsis
keywords: 11βHSD-2; 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; ANI; ANOVA; Adrenal steroids; Aldosterone; Analysis of Variance; CBX; CHX; DAPI; ENaC; FK506 binding protein 51kDa; FKBP5; FKBP51; GILZ; GR; HEPES; Isc; MR; Mineralocorticoid; PBS; PBS-T; PEG300; TER; TEV; anisomycin; carbenoxolone; cycloheximide; diamidino-2-phenylindole; distal colon; epithelial Na(+) channel; glucocorticoid receptor; glucocorticoid-induced leucine zipper; mineralocorticoid receptor; phosphate-buffered saline; phosphate-buffered saline+0.1% Tween 20; polyethylene glycol 300; serum and glucocorticoid-regulated kinase 1; sgk-1; short circuit current; transepithelial resistance; transepithelial voltage; type 2 11-beta-hydroxysteroid dehydrogenase