Journal article

Publication year: 2011

Pages: 175-183

Journal: Biochemical Pharmacology

Volume number: 82

Issue number: 2

ISSN: 0006-2952

Open access status: Green

DOI Link: https://doi.org/10.1016/j.bcp.2011.04.006

Publisher: Elsevier

Abstract: 
Convincing evidence from studies with peroxisome proliferator-activated receptor (PPAR)α-deficient mice suggested that the carnitine biosynthetic enzyme γ-butyrobetaine dioxygenase (BBD) is regulated by PPARα. However, the identification of BBD as a direct PPARα target gene as well as its exact regulation remained to be demonstrated. In silico-analysis of the mouse BBD promoter revealed seven putative peroxisome proliferator response elements (PPRE) with high similarity to the consensus PPRE. Luciferase reporter gene assays using mutated and non-mutated serial 5'-truncation BBD promoter reporter constructs revealed that one PPRE located at -75 to -87 relative to the transcription start site in the proximal BBD promoter is probably functional. Using gel shift assays we observed in vitro-binding of PPARα/RXRα heterodimer to this PPRE confirming that it is functional. In conclusion, the present study clearly shows that mouse BBD is a direct PPARα target gene and that transcriptional up-regulation of mouse BBD by PPARα is likely mediated by binding of the PPARα/RXR heterodimer to one PPRE located in its proximal promoter region. The results confirm emerging evidence from recent studies that PPARα plays a key role in the regulation of carnitine homeostasis by controlling genes involved in both, carnitine synthesis and carnitine uptake.

Harvard Citation style: Wen, G., Kühne, H., Rauer, C., Ringseis, R. and Eder, K. (2011) Mouse gamma-butyrobetaine dioxygenase is regulated by peroxisome proliferator-activated receptor alpha through a PPRE located in the proximal promoter, Biochemical Pharmacology, 82(2), pp. 175-183. https://doi.org/10.1016/j.bcp.2011.04.006

APA Citation style: Wen, G., Kühne, H., Rauer, C., Ringseis, R., & Eder, K. (2011). Mouse gamma-butyrobetaine dioxygenase is regulated by peroxisome proliferator-activated receptor alpha through a PPRE located in the proximal promoter. Biochemical Pharmacology. 82(2), 175-183. https://doi.org/10.1016/j.bcp.2011.04.006