Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/11310
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Type: Journal article
Title: Regulation of rat pyruvate carboxylase gene expression by alternate promoters during development in genetically obese rats and in insulin-secreting cells
Author: Jitrapakdee, S.
Gong, Q.
MacDonald, M.
Wallace, J.
Citation: Journal of Biological Chemistry, 1998; 273(51):34422-34428
Issue Date: 1998
ISSN: 0021-9258
1083-351X
Statement of
Responsibility: 
Sarawut Jitrapakdee, Qiuming Gong, Michael J. MacDonald, and John C. Wallace
Abstract: 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.
Keywords: Liver; Islets of Langerhans; Cell Line; Tumor Cells, Cultured; Fetus; Animals; Rats; Rats, Mutant Strains; Rats, Sprague-Dawley; Obesity; Insulin; Isoenzymes; Pyruvate Carboxylase; Protein Biosynthesis; Transcription, Genetic; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; Aging; Promoter Regions, Genetic; Insulin Secretion
Rights: The American Society for Biochemistry and Molecular Biology, Inc.
RMID: 0030004394
DOI: 10.1074/jbc.273.51.34422
Appears in Collections:Biochemistry publications

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