n-6 PUFAs downregulate expression of the tricarboxylate carrier in rat liver by transcriptional and posttranscriptional mechanisms.
The tricarboxylate (citrate) carrier (TCC), a protein of the mitochondrial inner membrane, is an obligatory component of the shuttle system by which mitochondrial acetyl-CoA is transported into the cytosol, where lipogenesis occurs. The aim of this study was to investigate the molecular basis for the regulation of TCC gene expression by a high-fat, n-6 PUFA-enriched diet. Rats received for up to 4 weeks a diet enriched with 15% safflower oil (SO), which is high in linoleic acid (70.4%). We found a gradual decrease of TCC activity and a parallel decline in the abundance of TCC mRNA, the maximum effect occurring after 4 weeks of treatment. At this time, the estimated half-life of TCC mRNA was the same in the hepatocytes from rats on both diets, whereas the transcriptional rate of TCC mRNA, tested by nuclear run-on assay, was reduced by approximately 38% in the rats on the SO-enriched diet. The RNase protection assay showed that the ratio of mature to precursor RNA, measured in the nuclei, decreased with the change to the n-6 PUFA diet. These results suggest that administration of n-6 PUFAs to rats leads to changes not only in the transcriptional rate of the TCC gene but also in the processing of the nuclear precursor for TCC RNA.
Siculella
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Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Laboratorio di Biochimica, Università di Lecce, I-73100 Lecce, Italy.
Damiano
F
F
Sabetta
S
S
Gnoni
G V
GV
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000737:chemistry / Q000378:metabolism; D012322:RNA Precursors / Q000032:analysis / Q000187:drug effects; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D020871:RNA Stability; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012450:Safflower Oil / Q000008:administration & dosage / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*
D002352:Carrier Proteins; D043371:Fatty Acids, Omega-6; D012322:RNA Precursors; D012333:RNA, Messenger; C020723:citrate-binding transport protein; D012450:Safflower Oil