Journalartikel

Jahr der Veröffentlichung: 2012

Seiten: 357-365

Zeitschrift: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Bandnummer: 1819

Heftnummer: 5

ISSN: 1874-9399

DOI Link: https://doi.org/10.1016/j.bbagrm.2012.01.004

Verlag: Elsevier

Abstract: 

Genes involved in carnitine uptake and synthesis, such as organic cation transporter-2 (OCTN2) and gamma-butyrobetaine dioxygenase (BBD), have been shown to be regulated by peroxisome proliferator-activated receptor (PPAR)alpha directly. Whether other genes encoding enzymes involved in the carnitine synthesis pathway, such as 4-N-trimethylaminobutyraldehyde dehydrogenase (TMABA-DH) and trimethyllysine dioxygenase (TMLD), are also direct PPAR alpha target genes is less clear. In silico-analysis of the mouse TMLD promoter and first intron and the TMABA-DH promoter revealed several putative peroxisome proliferator response elements (PPRE) with high similarity to the consensus PPRE. Luciferase reporter gene assays using either a 2 kb TMLD promoter or a 4 kb TMLD first intron reporter constructs revealed no functional PPRE. In contrast, reporter gene assays using wild-type and mutated 5'-truncation TMABA-DH promoter reporter constructs showed that one PPRE located at position - 132 in the proximal promoter is probably functional. Using gel shift assays we observed in vitro-binding of PPAR alpha to this PPRE. Moreover, using chromatin immunoprecipitation assays we found that PPAR alpha also binds in vivo to a nucleotide sequence spanning the PPRE at - 132, which confirms that this PPRE is functional. In conclusion, the present study shows that the mouse TMABA-DH gene is a direct PPAR alpha target gene. Together with the recent identification of the mouse BBD and the mouse OCTN2 genes as PPAR alpha target genes this finding confirm that PPAR alpha plays a key role in the regulation of carnitine homeostasis by controlling genes involved in carnitine synthesis and carnitine uptake.

Harvard-Zitierstil: Wen, G., Ringseis, R., Rauer, C. and Eder, K. (2012) The mouse gene encoding the carnitine biosynthetic enzyme 4-N-trimethylaminobutyraldehyde dehydrogenase is regulated by peroxisome proliferator-activated receptor α, Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 1819(5), pp. 357-365. https://doi.org/10.1016/j.bbagrm.2012.01.004

APA-Zitierstil: Wen, G., Ringseis, R., Rauer, C., & Eder, K. (2012). The mouse gene encoding the carnitine biosynthetic enzyme 4-N-trimethylaminobutyraldehyde dehydrogenase is regulated by peroxisome proliferator-activated receptor α. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1819(5), 357-365. https://doi.org/10.1016/j.bbagrm.2012.01.004