Selective induction of Na,K-ATPase alpha 3 subunit mRNA abundance in cardiac myocytes by retinoic acid

Retinoic acid (RA) is a high affinity ligand for a nuclear receptor which r egulates transcription in target cells. Specific effects of RA on cardiac d evelopment and myocardial cell hypertrophy have been demonstrated; however, little information exists concerning RA-mediated regulation of cardiac gen es. This study was initiated to investigate whether RA regulates Na,K-ATPas e subunit gene expression in primary cultures of neonatal rat cardiac myocy tes. Northern blot analyses demonstrated that NA, K-ATPase alpha 3 subunit mRNA content was stimulated three-fold by RA. The effect of RA on alpha 3 s ubunit gene expression was selective as RA treatment had no effect on eithe r Na,K-ATPase alpha 1, alpha 2 or beta 1 subunit mRNAs, A stimulatory effec t of RA on Na,K-ATPase alpha 3 gene transcription was not evident in either transient transfection or nuclear run-on studies, suggesting that augmenta tion of alpha 3 mRNA content by RA was due to a post-transcriptional mechan ism. Finally, RA diminished the magnitude of the thyroid hormone (TS)-media ted increase in Na,K-ATPase beta 1 subunit mRNA, while EW had no effect on the stimulation of alpha 3 mRNA content by T3. (C) 1998 Academic Press.