Nutritional Regulation of the Glucose-6-Phosphate Dehydrogenase Gene Is Mediated by a Nuclear Posttranscriptional Mechanism

Hodge, Deborah L.; Salati, Lisa M.

doi:10.1006/abbi.1997.0373

Cited by 27 publications

(45 citation statements)

References 39 publications

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“…The increase in ME activity in response to a high-carbohydrate diet is accounted for by alterations in the stability of the cytoplasmic mRNA and not by changes in the transcriptional activity of this gene (35). PUFA suppression of G6PD involves a posttranscriptional mechanism that is quite different in that it occurs in the nucleus early after transcription and could be ascribed to a differential partitioning of pre-mRNA into various nuclear compartments (12,40,41).…”

Section: Discussionmentioning

confidence: 99%

“…Different mechanisms are responsible for the regulation of the lipogenic enzymes at the molecular level. The PUFA-mediated inhibition of ACC, FAS, L-PK, stearoyl-CoA desaturase (SCD-1), and, in part, S14 protein occurs at the transcriptional level (6)(7)(8)(9)(10)(11), whereas PUFA suppression of G6PD and ME is thought to occur through a posttranscriptional mechanism (1,5,12).…”

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confidence: 99%

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

Siculella

Damiano

Sabetta

et al. 2004

Journal of Lipid Research

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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 ‫ف‬ 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, L., F. Damiano, S. Sabetta, and G. V. Gnoni. n-6 PUFAs downregulate expression of the tricarboxylate carrier in rat liver by transcriptional and posttranscriptional mechanisms. J. Lipid Res. 2004. 45: 1333-1340.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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

Siculella

Damiano

Sabetta

et al. 2004

Journal of Lipid Research

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“…G6PD was activated at the post-translational level because G6PD protein and G6PD mRNA levels were similar in (pre)neoplastic lesions, extralesional liver parenchyma, and normal parenchyma. Thus far, induction of G6PD activity was demonstrated at the gene level, e.g., as a consequence of hormone treatment (Lombardi et al 2000), oxidative stress (Díez-Fernández et al 1996;Ursini et al 1997;Tian et al 1998Tian et al ,1999Salvemini et al 1999), treatment with NAD ϩ precursors (Yan et al 1999), and in liver cirrhosis (Sanz et al 1997), whereas post-transcriptional regulation was described to be caused by nutrition (Stabile et al 1996(Stabile et al ,1998Hodge and Salati 1997;Amir-Ahmady and Salati 2001). Rapid upregulation of G6PD activity at the post-translational level was demonstrated after treatment of animals or cells with hormones (Lombardi et al 2000), GSH-depleting agents (Salvemini et al 1999), and growth factors (Stanton et al 1991).…”

Section: Discussionmentioning

confidence: 99%

Post-translational Regulation of Glucose-6-phosphate Dehydrogenase Activity in (Pre)neoplastic Lesions in Rat Liver

Frederiks

Bosch

Jong

et al. 2003

J Histochem Cytochem.

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S U M M A R Y Glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) is the key regulatory enzyme of the pentose phosphate pathway and produces NADPH and riboses. In this study, the kinetic properties of G6PD activity were determined in situ in chemically induced hepatocellular carcinomas, and extralesional and control parenchyma in rat livers and were directly compared with those of the second NADPH-producing enzyme of the pentose phosphate pathway, phosphogluconate dehydrogenase (PGD). Distribution patterns of G6PD activity, protein, and mRNA levels were also compared to establish the regulation mechanisms of G6PD activity. In (pre)neoplastic lesions, the V max of G6PD was 150-fold higher and the K m for G6P was 10-fold higher than in control liver parenchyma, whereas in extralesional parenchyma, the V max was similar to that in normal parenchyma but the K m was fivefold lower. This means that virtual fluxes at physiological substrate concentrations are 20-fold higher in lesions and twofold higher in extralesional parenchyma than in normal parenchyma. The V max of PGD was fivefold higher in lesions than in normal and extralesional liver parenchyma, whereas the K m was not affected. Amounts of G6PD protein and mRNA were similar in lesions and in extralesional liver parenchyma. These results demonstrate that G6PD is strongly activated post-translationally in (pre)neoplastic lesions to produce NADPH.

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“…Most of these enzymes are regulated either at transcriptional or at post-transcriptional steps. FAS [3,6], ACC [3,4] and stearoyl-CoA desaturase [7] are dietary regulated at transcriptional level, whereas PUFA regulation of malic enzyme occurs by changes in mRNA stability [3] and glucose-6-phosphate dehydrogenase is controlled by a posttranscriptional mechanism [8].…”

Section: Introductionmentioning

confidence: 99%

Different dietary fatty acids have dissimilar effects on activity and gene expression of mitochondrial tricarboxylate carrier in rat liver

et al. 2004

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The tricarboxylate carrier (TCC), an integral protein of the mitochondrial inner membrane, transports mitochondrial acetyl-CoA into the cytosol, where lipogenesis occurs. We investigated in rat liver mitochondria the effect of diets enriched with saturated fatty acids (beef tallow, BT), monounsaturated fatty acids (olive oil, OO) or n À 3 polyunsaturated fatty acids (fish oil, FO), respectively, on the activity and expression of TCC. TCC activity decreased, in parallel with TCC mRNA abundance, only upon FO-feeding. The TCC transcription rate, mRNA turnover and RNA processing indicated that FO administration regulates TCC gene at transcriptional and post-transcriptional steps, whereas BT-and OO-feeding do not seem to affect either TCC activity or gene expression.

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Nutritional Regulation of the Glucose-6-Phosphate Dehydrogenase Gene Is Mediated by a Nuclear Posttranscriptional Mechanism

Cited by 27 publications

References 39 publications

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

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

Post-translational Regulation of Glucose-6-phosphate Dehydrogenase Activity in (Pre)neoplastic Lesions in Rat Liver

Different dietary fatty acids have dissimilar effects on activity and gene expression of mitochondrial tricarboxylate carrier in rat liver

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