Identification by differential display of the IF1 inhibitor peptide of ATP synthase/ATPase as a gene inducible in rat liver by pregnenolone 16alpha-carbonitrile.
The synthetic steroid, pregnenolone-16alpha-carbonitrile (PCN), activates hepatic metabolism and elimination of xenobiotics mediated by its interaction with the PXR, a nuclear receptor that binds PCN and such glucocorticoids as dexamethasone (Dex). We used mRNA differential display to define further the domain of genes under the control of PCN/PXR. We found 76 cDNA fragments representing mRNAs differentially expressed in the liver of rats treated with PCN or Dex. Sequence analysis of one of these revealed a PCN induced cDNA fragment as IF1, an inhibitor peptide of ATP synthase/ATPase complex. Northern blot analysis revealed that IF1 was detectable in untreated liver and was induced 2-3 fold following treatment with PCN. IF1 mRNA was not detected in lung, heart, kidney, or testes of control or PCN treated rats. We conclude that IF1 inhibitor peptide is a novel representative of an apparently large set of previously unrecognized genes coordinately controlled by the PCN/PXR system to maintain homeostasis during toxic stress.
Jiménez
B D
BD
Section of Medical Toxicology, School of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Quattrochi
L C
LC
Yockey
C B
CB
Guzelian
P S
PS
D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097795:ATPase Inhibitory Protein
D000251:Adenosine Triphosphatases; D003907:Dexamethasone; D005938:Glucocorticoids; D011285:Pregnenolone Carbonitrile; D011506:Proteins; D006180:Proton-Translocating ATPases; D012333:RNA, Messenger; D000097795:ATPase Inhibitory Protein