HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M400061-JLR200v1 45/7/1333    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Siculella, L. Articles by Gnoni, G. V. Search for Related Content PubMed PubMed Citation Articles by Siculella, L. Articles by Gnoni, G. V. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 45, 1333-1340, July 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

n-6 PUFAs downregulate expression of the tricarboxylate carrier in rat liver by transcriptional and posttranscriptional mechanisms

L. Siculella, F. Damiano, S. Sabetta and G. V. Gnoni¹

Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Laboratorio di Biochimica, Università di Lecce, I-73100 Lecce, Italy

¹ To whom correspondence should be addressed. e-mail: gabriele.gnoni{at}unile.it

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 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.

Abbreviations: ACC, acetyl-CoA carboxylase; G6PD, glucose-6-phosphate dehydrogenase; ME, malic enzyme; L-PK, pyruvate kinase; SCD-1, stearoyl-CoA desaturase; SO, safflower oil; TCC, tricarboxylate carrier

Supplementary key words gene modulation • lipogenesis • mRNA turnover • mitochondria • polyunsaturated fatty acids • ribonuclease protection assay • run-on assay • safflower oil

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. Natali, L. Siculella, S. Salvati, and G. V. Gnoni Oleic acid is a potent inhibitor of fatty acid and cholesterol synthesis in C6 glioma cells J. Lipid Res., September 1, 2007; 48(9): 1966 - 1975. [Abstract] [Full Text] [PDF]

				W. Szeszel-Fedorowicz, I. Talukdar, B. N. Griffith, C. M. Walsh, and L. M. Salati An Exonic Splicing Silencer Is Involved in the Regulated Splicing of Glucose 6-Phosphate Dehydrogenase mRNA J. Biol. Chem., November 10, 2006; 281(45): 34146 - 34158. [Abstract] [Full Text] [PDF]

				L. Siculella, S. Sabetta, A. M. Giudetti, and G. V. Gnoni Hypothyroidism Reduces Tricarboxylate Carrier Activity and Expression in Rat Liver Mitochondria by Reducing Nuclear Transcription Rate and Splicing Efficiency J. Biol. Chem., July 14, 2006; 281(28): 19072 - 19080. [Abstract] [Full Text] [PDF]