Dexamethasone markedly induces Na,K-ATPase mRNA beta 1 in a rat liver cell line.
Exposure of Clone 9 cells, a "nontransformed" rat liver cell line, to 10(-8) M dexamethasone resulted at 3 h in 1.8 +/- 0.2- and 40 +/- 5-fold increases in mRNA alpha 1 and mRNA beta 1 content, respectively, an effect that was not mimicked by 10(-8) M aldosterone. The increments in mRNA alpha 1 and mRNA beta 1 abundances in total cell RNA were half-maximal at 5 x 10(-9) M dexamethasone and persisted for more than 24 h. Na,K-ATPase activity, however, increased only slightly (by 9%) at 24 h. The induction of mRNA beta 1 by dexamethasone was not prevented by the presence of cycloheximide. mRNA beta 1 abundance increased earlier in the nuclear RNA pool (becoming apparent within 45 min) than in the cytoplasmic RNA pool, consistent with a precursor-product relationship. Moreover, putative pre-mRNA beta 1 bands of approximately 4,600 and approximately 12,000 nucleotides accumulated in the nRNA pool after 1 h of exposure to dexamethasone. Incubation in the presence of dexamethasone for 3 h enhanced the incorporation of [3H]uridine into total cell mRNA alpha 1 and mRNA beta 1 by 1.3- and 12-fold, respectively. In nuclear run-on assays, however, transcription of mRNA alpha 1 and mRNA beta 1 was not altered after 30 min of exposure to 10(-8) M dexamethasone. The abundance of mRNA beta 1 in rat liver also increased markedly (greater than 30-fold) in rats treated with the hormone for 6 h. We conclude that dexamethasone causes an induction of Na,K-ATPase subunit mRNAs, an effect that is markedly greater for mRNA beta 1 than for mRNA alpha 1. The increases in subunit mRNA content, however, are associated with, at most, a small increase in Na,K-ATPase activity, suggesting that the increments in mRNA abundances, especially that of mRNA beta 1, do not play a determining role in the regulation of Na,K-ATPase activity in these cells.
Bhutada
A
A
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Wassynger
W W
WW
Ismail-Beigi
F
F
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014529:Uridine / Q000378:metabolism
D012333:RNA, Messenger; D003907:Dexamethasone; D000254:Sodium-Potassium-Exchanging ATPase; D014529:Uridine