Effect of altered acid-base balance and of various agonists on levels of renal glutamate dehydrogenase mRNA.
Rat kidney contains 3.5-kb and 2.8-kb mRNAs that encode for glutamate dehydrogenase (GDH). The levels of both mRNAs are increased gradually after onset of chronic metabolic acidosis and reach a maximum induction of 2.5-fold after 7 days. In contrast, during recovery from chronic acidosis, the levels of the GDH mRNAs are returned to normal within 1 day. The development of an acute metabolic acidosis causes a more rapid induction of GDH mRNA. This increase occurs after a 7-h lag and plateaus after 18 h at a level that is threefold greater than normal. A very similar profile was observed after the transfer of LLC-PK-F+ cells from normal medium to an acidic medium containing 10 mM bicarbonate and adjusted to pH 6.9. However, the transfer of cells from acidic to normal medium caused an immediate and rapid [half-life (t) = 1 h] decrease in GDH mRNA. The apparent half-lives of GDH mRNA were measured by treating cells grown in normal (t = 4 h) and acidic media (t = 12 h) with actinomycin D. Thus, increased stability may account for the induction of GDH mRNA that occurs during growth in response to acidosis. The levels of GDH mRNA are independently affected by changes in medium pH or bicarbonate concentration. The levels of GDH mRNA are also increased by treating cells with adenosine 3',5'-cyclic monophosphate, epinephrine, triiodothyronine, or retinoic acid, whereas treatment with angiotensin II, vasopressin, phorbol 12-myristate 13-acetate, or cycloheximide did not produce an increase. The inductive effect of dexamethasone, which is observed in vivo, is not reproduced in the LLC-PK-F+ cells.
Kaiser
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S
Department of Biochemistry, Colorado State University, Fort Collins 80523.
Hwang
J J
JJ
Smith
H
H
Banner
C
C
Welbourne
T C
TC
Curthoys
N P
NP
D000136:Acid-Base Equilibrium; D000199:Actins / Q000235:genetics; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002460:Cell Line; D003609:Dactinomycin / Q000494:pharmacology; D005969:Glutamate Dehydrogenase / Q000235:genetics*; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D000199:Actins; D001639:Bicarbonates; D012333:RNA, Messenger; D003609:Dactinomycin; D005969:Glutamate Dehydrogenase