Mechanism of altered renal glutaminase gene expression in response to chronic acidosis.
Increased rat renal ammoniagenesis is sustained during chronic metabolic acidosis by the cell-specific induction of the regulatory enzymes of glutamine catabolism and of gluconeogenesis. A glutaminase-specific cDNA hybridizes to 6.0- and 3.4-kb mRNAs that are contained in total or poly(A)+ RNA isolated from rat kidney. When translated in a rabbit reticulocyte lysate, each of the fractionated mRNAs produces the 72-kDa precursor of the mitochondrial glutaminase. The levels of both mRNAs are increased 5-fold within 1 day following onset of chronic acidosis and reach a maximum (8-fold) after 5 days. During recovery from chronic acidosis, the levels of the glutaminase mRNAs are returned to normal within 1 day. The observed changes in mRNA levels correlate with equivalent changes in the relative levels of translatable glutaminase mRNA. Nuclear run-on assays indicate that the rate of transcription of the renal phosphoenolpyruvate carboxykinase gene is increased and decreased in response to onset and recovery from chronic acidosis, respectively. In contrast, the rates of transcription of the glutaminase and beta-actin genes are unaffected by alterations in acid-base balance. Thus, the increase in renal glutaminase activity during chronic acidosis results from an equivalent increase in the levels of total and translatable glutaminase mRNAs which apparently results from an increased stability of the glutaminase mRNA.
Hwang
J J
JJ
Department of Biochemistry, Colorado State University, Fort Collins 80523.
Perera
S
S
Shapiro
R A
RA
Curthoys
N P
NP
D000138:Acidosis / Q000201:enzymology* / Q000235:genetics; D000199:Actins / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D002908:Chronic Disease; D004790:Enzyme Induction; D005972:Glutaminase / Q000096:biosynthesis / Q000235:genetics*; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic
D000199:Actins; D012333:RNA, Messenger; D005972:Glutaminase; D010729:Phosphoenolpyruvate Carboxykinase (GTP)