Glucocorticoid regulation of genes in the amiloride-sensitive sodium transport pathway by semicircular canal duct epithelium of neonatal rat
| Autor: | Joel D. Sanneman, Youping Deng, Satyanarayana R. Pondugula, Zuhal Ergonul, Nithya N. Raveendran, Jun Chen, Lawrence G. Palmer, Daniel C. Marcus |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Physiology Nedd4 Ubiquitin Protein Ligases Ubiquitin-Protein Ligases Sodium chemistry.chemical_element Protein Serine-Threonine Kinases Biology Epithelium Cholangiocyte Immediate-Early Proteins Amiloride Receptors Glucocorticoid Glucocorticoid receptor Internal medicine Genetics medicine Animals Dimethyl Sulfoxide Inner ear RNA Messenger Rats Wistar Epithelial Sodium Channels Receptor Cation Transport Proteins Glucocorticoids Cells Cultured Endosomal Sorting Complexes Required for Transport Semicircular canal Biological Transport Semicircular Canals Rats Endocrinology medicine.anatomical_structure Animals Newborn Gene Expression Regulation chemistry 11-beta-Hydroxysteroid Dehydrogenases Glucocorticoid medicine.drug |
| Zdroj: | Physiological Genomics. 24:114-123 |
| ISSN: | 1531-2267 1094-8341 |
| DOI: | 10.1152/physiolgenomics.00006.2005 |
| Popis: | The lumen of the inner ear has an unusually low concentration of endolymphatic Na+, which is important for transduction processes. We have recently shown that glucocorticoid receptors (GR) stimulate absorption of Na+by semicircular canal duct (SCCD) epithelia. In the present study, we sought to determine the presence of genes involved in the control of the amiloride-sensitive Na+transport pathway in rat SCCD epithelia and whether their level of expression was regulated by glucocorticoids using quantitative real-time RT-PCR. Transcripts were present for α-, β-, and γ-subunits of the epithelial sodium channel (ENaC); the α1-, α3-, β1-, and β3-isoforms of Na+-K+-ATPase; inwardly rectifying potassium channels [IC50of short circuit current ( Isc) for Ba2+: 210 μM] Kir2.1, Kir2.2, Kir2.3, Kir2.4, Kir3.1, Kir3.3, Kir4.1, Kir4.2, Kir5.1, and Kir7.1; sulfonyl urea receptor 1 (SUR1); GR; mineralocorticoid receptor (MR); 11β-hydroxysteroid dehydrogenase (11β-HSD) types 1 and 2; serum- and glucocorticoid-regulated kinase 1 (Sgk1); and neural precursor cell-expressed developmentally downregulated 4-2 (Nedd4-2). On the other hand, transcripts for the α4-subunit of Na+-K+-ATPase, Kir1.1, Kir3.2, Kir3.4, Kir6.1, Kir6.2, and SUR2 were found to be absent, and Iscwas not inhibited by glibenclamide. Dexamethasone (100 nM for 24 h) not only upregulated the transcript expression of α-ENaC (∼4-fold), β2-subunit (∼2-fold) and β3-subunit (∼8-fold) of Na+-K+-ATPase, Kir2.1 (∼5-fold), Kir2.2 (∼9-fold), Kir2.4 (∼3-fold), Kir3.1 (∼ 3- fold), Kir3.3 (∼2-fold), Kir4.2 (∼3-fold ), Kir7.1 (∼2-fold), Sgk1 (∼4-fold), and Nedd4-2 (∼2-fold) but also downregulated GR (∼3-fold) and 11β-HSD1 (∼2-fold). Expression of GR and 11β-HSD1 was higher than MR and 11β-HSD2 in the absence of dexamethasone. Dexamethasone altered transcript expression levels (α-ENaC and Sgk1) by activation of GR but not MR. Proteins were present for the α-, β-, and γ-subunits of ENaC and Sgk1, and expression of α- and γ-ENaC was upregulated by dexamethasone. These findings are consistent with the genomic stimulation by glucocorticoids of Na+absorption by SCCD and provide an understanding of the therapeutic action of glucocorticoids in the treatment of Meniere's disease. |
| Databáze: | OpenAIRE |
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