Hormonal induction of hepatic mitochondrial ornithine/citrulline transporter mRNA.
The urea cycle, which involves enzymes located in both the mitochondrion and cytoplasm, requires transport of ornithine and citrulline across the mitochondrial membrane by the ornithine/citrulline antiporter ORNT1. Expression of the urea cycle enzymes can change dramatically in response to hormones, but it is not known whether ORNT1 expression also is hormonally regulated. This study therefore tested the hypothesis that ORNT1 mRNA levels in hepatocytes are induced by cAMP and glucocorticoid as are the urea cycle enzyme mRNAs. ORNT1 mRNA was rapidly induced by a cAMP analog and dexamethasone in cultured rat hepatocytes and there was a strong synergistic response to a combination of these agents. Ongoing protein synthesis was required for induction of ORNT1 mRNA by dexamethasone but not by cAMP, suggesting that the dexamethasone response required an accessory factor. Thus, hormonal regulation of ORNT1 mRNA in hepatocytes is coordinated with that of mRNAs encoding the urea cycle enzymes.
Morris
Sidney M
SM
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, W1255 Biomedical Science Tower, PA 15206, USA. smorris@pitt.edu
Kepka-Lenhart
Diane
D
D026923:Amino Acid Transport Systems, Basic; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D002956:Citrulline / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D008954:Models, Biological; D009952:Ornithine / Q000378:metabolism; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015533:Transcriptional Activation; D014508:Urea / Q000378:metabolism
D026923:Amino Acid Transport Systems, Basic; D005938:Glucocorticoids; D033681:Mitochondrial Membrane Transport Proteins; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D012333:RNA, Messenger; C442901:SLC25A15 protein, human; D002956:Citrulline; D003907:Dexamethasone; D014508:Urea; D003513:Cycloheximide; D000242:Cyclic AMP; D009952:Ornithine