Evidence for post-transcriptional regulation of Na,K-ATPase by prostaglandin E₁

The stimulatory effect of PGE₁ on the activity of the Na,K-ATPase in MDCK cells is associated with an increase in the rate of transcription of the Na,K-ATPase β1 subunit gene and an increase in the rate of biosynthesis of the Na,K-ATPase [M.L. Taub, Y. Wang, I.S. Yang, P. Fiorella, S.M. Lee, Regulation of the Na,K-ATPase activity of Madin-Darby canine kidney cells in defined medium by prostaglandin E1 and 8-bromocyclic AMP, J. Cell. Physiol. 151 (1992) 337-346]. In order to further define the molecular mechanisms, transient transfection and biosynthesis studies were conducted with dibutyryl cAMP resistant (DB^r) MDCK cells, defective in cAMP dependent protein kinase, and PGE₁ independent (PGE₁ Ind) MDCK cells with elevated intracellular cAMP. Transient transfection studies with the human Na,K-ATPase β1 promoter/luciferase construct, pHβ1-1141 Luc [J. Feng, J. Orlowski, J.B. Lingrel, Identification of a functional thyroid hormone response element in the upstream flanking region of the human Na,K-ATPase beta 1 gene, Nucleic Acids Res. 21 (1993) 2619-2626], showed that the stimulatory effect of PGE₁ and 8Br-cAMP on β1 subunit gene transcription is retained in the DB^r and PGE₁ independent variants. However, the stimulatory effect of PGE₁ and 8Br-cAMP on Na,K-ATPase biosynthesis was lost in DB^r (unlike PGE₁ Ind) variants. These results can be explained by a defect in post-transcriptional regulation.