Selective Induction of Na,K-ATPaseα3 Subunit mRNA Abundance in Cardiac Myocytes by Retinoic Acid

Retinoic acid (RA) is a high affinity ligand for a nuclear receptor which regulates transcription in target cells. Specific effects of RA on cardiac development and myocardial cell hypertrophy have been demonstrated; however, little information exists concerning RA-mediated regulation of cardiac genes. This study was initiated to investigate whether RA regulates Na,K-ATPase subunit gene expression in primary cultures of neonatal rat cardiac myocytes. Northern blot analyses demonstrated that NA, K-ATPaseα3 subunit mRNA content was stimulated three-fold by RA. The effect of RA onα3 subunit gene expression was selective as RA treatment had no effect on either Na,K-ATPaseα1,α2 orβ1 subunit mRNAs. A stimulatory effect of RA on Na,K-ATPaseα3 gene transcription was not evident in either transient transfection or nuclear run-on studies, suggesting that augmentation ofα3 mRNA content by RA was due to a post-transcriptional mechanism. Finally, RA diminished the magnitude of the thyroid hormone (T3)-mediated increase in Na,K-ATPaseβ1 subunit mRNA, while RA had no effect on the stimulation ofα3 mRNA content by T3.