Glucose Regulates the Expression of the Apolipoprotein A5 Gene
Autor: | Emmanuelle Moitrot, Audrey Helleboid-Chapman, Jamila Fruchart-Najib, Heidelinde Jakel, Len A. Pennacchio, Corinne Rommens, Jean-Charles Fruchart, Maxime Nowak |
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Rok vydání: | 2008 |
Předmět: |
Time Factors
Transcription Genetic Phosphatase USF1 Biology Cell Line Structural Biology Cell Line Tumor Protein Phosphatase 1 Animals Humans Gene silencing Glucose homeostasis Protein Phosphatase 2 RNA Messenger Enzyme Inhibitors Promoter Regions Genetic Molecular Biology Gene Apolipoproteins A Regulation of gene expression Dose-Response Relationship Drug Molecular biology Rats Chromatin Enzyme Activation Glucose Gene Expression Regulation Apolipoprotein A-V Hepatocytes biology.protein Upstream Stimulatory Factors Glycolysis Chromatin immunoprecipitation Protein Binding |
Zdroj: | Journal of Molecular Biology. 380:789-798 |
ISSN: | 0022-2836 |
Popis: | The apolipoprotein A5 gene (APOA5) is a key player in determining triglyceride concentrations in humans and mice. Since diabetes is often associated with hypertriglyceridemia, this study explores whether APOA5 gene expression is regulated by alteration in glucose homeostasis and the related pathways. d-Glucose activates APOA5 gene expression in a time- and dose-dependent manner in hepatocytes, and the glycolytic pathway involved was determined using d-glucose analogues and metabolites. Together, transient transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays show that this regulation occurs at the transcriptional level through an increase of USF1/2 binding to an E-box in the APOA5 promoter. We show that this phenomenon is not due to an increase of mRNA or protein expression levels of USF. Using protein phosphatases 1 and 2A inhibitor, we demonstrate that d-glucose regulates the APOA5 gene via a dephosphorylation mechanism, resulting in an enhanced USF1/2-promoter binding. Last, subsequent suppressions of USF1/2 and phosphatases mRNA through siRNA gene silencing abolished the regulation. We demonstrate that the APOA5 gene is up regulated by d-glucose and USF through phosphatase activation. These findings may provide a new cross-talk between glucose and lipid metabolism. |
Databáze: | OpenAIRE |
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