Transcriptional regulation of the human Na/K ATPase via the human mineralocorticoid receptor.
The mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) are members of the steroid/thyroid hormone receptor superfamily of ligand inducible transcription factors and have been shown to bind the glucocorticoid response element (GRE). Sodium-potassium ATPase (Na/KATPase) is a major target of mineralocorticoids. Both aldosterone and glucocorticoids activate the human Na/K ATPase alpha1 subunit and beta1 subunit genes transcriptionally. However, the mechanisms of corticosteroid regulation of mammalian Na/K ATPase subunit gene expression are not known. In this investigation, we report for the first time that cell lines (T-84 and 293) express endogenous MR by RT-PCR message expression. However, the protein product was not expressed as determined by western blot analyses. In transactivation studies of MR with GRE31, we detected MR expression at low concentrations of aldosterone. We also performed Northern blot and nuclear run-off transcription assays to further confirm that the regulation is transcriptional. We conclude that the transcriptional regulation of the human Na/K ATPase alpha1 and beta1 subunits by aldosterone occurs via the involvement of the MR.
Kolla
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V
Department of Biochemistry and Molecular Pharmacology, Jefferson Medical College, Thomas Jefferson University, Piladelphia 19107, USA.
Litwack
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G
D000450:Aldosterone / Q000494:pharmacology; D015152:Blotting, Northern; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D018161:Receptors, Mineralocorticoid / Q000032:analysis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects
D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D000254:Sodium-Potassium-Exchanging ATPase