The Rat Pyruvate Carboxylase Gene Structure

Jitrapakdee, Sarawut; Booker, Grant W.; Cassady, A. I.; Wallace, John C.

doi:10.1074/jbc.272.33.20522

Cited by 55 publications

(31 citation statements)

References 47 publications

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“…The presence of a putative fat-specific element 1 on the proximal promoter (16) suggests that overexpression of PC might also be mediated through this motif, as occurs in the fatty acid synthetase gene (28). Insulin selectively inhibits the expression of the proximal promoter of rat PC (16). However, the activity of this promoter is increased in the adipose tissue of the obese Zucker rat (Fig.…”

Section: Discussionmentioning

confidence: 96%

“…Transcript C is the major transcript that is increased in both liver and adipose tissue of the obese rats, suggesting that the proximal promoter is transcriptionally activated during the lipogenic period. The presence of a putative fat-specific element 1 on the proximal promoter (16) suggests that overexpression of PC might also be mediated through this motif, as occurs in the fatty acid synthetase gene (28). Insulin selectively inhibits the expression of the proximal promoter of rat PC (16).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, semi-quantitative RT-PCR was also performed to identify which promoter of the PC gene was being used to control the expression. Two sense primers directed against the most 5Ј-untranslated region of class I (exon 1B) and class II (exon 1D) PC transcripts (12,16) and an antisense primer directed to a common coding region of the different transcripts were used to selectively amplify by PCR the 5Ј-ends of the different PC cDNA species (see Fig. 1).…”

Section: Developmental Regulation Of Pc Expression In Postnatal Ratmentioning

confidence: 99%

“…Two tissue-specific promoters are responsible for the production of two primary transcripts, which then are differentially spliced to five mature transcripts (16). Transcripts generated from the proximal promoter are restricted to gluconeogenic and lipogenic tissues, whereas transcripts generated from the distal promoter are expressed in a wide variety of tissues (12).…”

mentioning

confidence: 99%

“…Our studies on the isolation of cDNA (11) and the gene structure (16) of rat PC indicated that although there is only one copy of the PC gene (17), it generates several forms of PC mRNA, which diverge at their 5Ј-untranslated regions (UTR) but share the same open reading frame encoding a 1178-residue polypeptide (12). Two tissue-specific promoters are responsible for the production of two primary transcripts, which then are differentially spliced to five mature transcripts (16).…”

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confidence: 99%

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Regulation of Rat Pyruvate Carboxylase Gene Expression by Alternate Promoters during Development, in Genetically Obese Rats and in Insulin-secreting Cells

Jitrapakdee

Gong²,

MacDonald³

et al. 1998

Journal of Biological Chemistry

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A previous study on the gene structure of rat pyruvate carboxylase revealed that two tissue-specific promoters are responsible for the production of multiple transcripts with 5-end heterogeneity (Jitrapakdee, S., Booker, G. W., Cassady, A. I., and Wallace, J. C. (1997) J. Biol. Chem. 272, 20522-20530). Here we report transcription and translation regulation of pyruvate carboxylase (PC) expression during development and in genetically obese rats. The abundance of PC mRNAs was low in fetal liver but increased by 2-4-fold within 7 days after birth, concomitant with an 8-fold increase in the amount of immunoreactive PC and its activity and then decreased during the weaning period. Reverse transcriptase polymerase chain reaction analysis indicated that the proximal promoter was activated during the suckling period and reduced in activity at weaning. In genetically obese Zucker rats, adipose PC was 4 -5-fold increased, concomitant with a 5-6-fold increase in mRNA level. Reverse transcriptase-polymerase chain reaction analysis also showed that the proximal promoter was activated in the hyperlipogenic condition. Conversely, transcription of the proximal promoter was not detectable in various liver cell lines, suggesting that this promoter was not functional under cell culture conditions. In rat pancreatic islets and insulinoma cells, only transcripts D and E, generated from the distal promoter of the PC gene, were expressed. Glucose increased PC transcripts from the distal promoter when the insulinoma cells were maintained in 10 mM glucose. We conclude that the proximal promoter of the rat PC gene plays a major role in gluconeogenesis and lipogenesis, whereas the distal promoter is necessary for anaplerosis. In vitro translation and in vivo polysome profile analysis indicated that transcripts C and E were translated with similar translational efficiencies that are substantially greater than that of transcript D, suggesting that 5-untranslated regions play a role in translational control.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Developmental Regulation Of Pc Expression In Postnatal Ratmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Regulation of Rat Pyruvate Carboxylase Gene Expression by Alternate Promoters during Development, in Genetically Obese Rats and in Insulin-secreting Cells

Jitrapakdee

Gong²,

MacDonald³

et al. 1998

Journal of Biological Chemistry

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Effect of rosiglitazone on the differential expression of obesity and insulin resistance associated proteins in lep/lep mice

et al. 2003

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Peroxisome proliferator-activated receptors (PPARs) participate in the molecular mechanism of pathologies with altered lipid homeostasis such as type 2 diabetes or obesity. The insulin sensitizer drug, rosiglitazone, has been shown to bind and activate PPAR-gamma1 in adipocytes and PPAR-gamma2 in hepatocytes. The identification of new molecular targets associated with fatty acid oxidation and PPAR-gamma nuclear receptor regulation in insulin resistance tissues is a key research goal. In the present study, we have used a proteomic approach to identify such targets. Lean and obese C57 Bl/6J lep/lep mice were given BRL49653, rosiglitazone, 10 mg/kg diet, by dietary admixture for 7 days. Rosiglitazone normalized the impaired glucose tolerance and dyslipidemia in lep/lep mice but had no significant effect in the lean mice. Samples of liver, white and brown adipose tissue, and muscle proteins were obtained and 100 microg of proteins was arrayed by two-dimensional gel electrophoresis. Thirty-four polypeptides were differentially expressed (p < 0.05) between lep/lep and lean mice and eleven were significantly (p < 0.05) modulated by rosiglitazone treatment of the obese mice. None of the proteins was modulated by rosiglitazone treatment of the lean mice. The identity of these differentially expressed proteins was made using tandem mass spectrometric analysis and revealed components of fatty acid and carbohydrate metabolism as well as proteins with unknown function.

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Development of a Bicistronic Vector Driven by the Human Polypeptide Chain Elongation Factor 1α Promoter for Creation of Stable Mammalian Cell Lines That Express Very High Levels of Recombinant Proteins

Hobbs

Jitrapakdee

Wallace

1998

Biochemical and Biophysical Research Communications

244

167

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The Rat Pyruvate Carboxylase Gene Structure

Cited by 55 publications

References 47 publications

Regulation of Rat Pyruvate Carboxylase Gene Expression by Alternate Promoters during Development, in Genetically Obese Rats and in Insulin-secreting Cells

Regulation of Rat Pyruvate Carboxylase Gene Expression by Alternate Promoters during Development, in Genetically Obese Rats and in Insulin-secreting Cells

Effect of rosiglitazone on the differential expression of obesity and insulin resistance associated proteins in lep/lep mice

Development of a Bicistronic Vector Driven by the Human Polypeptide Chain Elongation Factor 1α Promoter for Creation of Stable Mammalian Cell Lines That Express Very High Levels of Recombinant Proteins

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