Functional characterization of a peroxisome proliferator response-element located in the intron 3 of rat peroxisomal thiolase B gene.

Expression of the rat peroxisomal 3-ketoacyl-CoA thiolase gene B is induced by peroxisome proliferators. Although a sequence element like a peroxisome proliferator-activated receptor (PPAR)-binding site is located in the promoter region of this gene, we previously found that this element is competent for the activation by hepatocyte nuclear factor-4, but not functional with PPARalpha. We describe here a new peroxisome proliferator-response element located in the intron 3 (+1422/+1434) that binds in vitro the PPARalpha/retinoid X receptor alpha heterodimer and confers the induction by PPARalpha in transfection assays. We propose a model of regulation of the rat thiolase B gene involving thos…

PPARs as physiological sensors of fatty acid metabolism molecular regulation in peroxisomes

NFY interacts with the promoter region of two genes involved in the rat peroxisomal fatty acid β-oxidation: the multifunctional protein type 1 and the 3-ketoacyl-CoA B thiolase

Abstract Background β-oxidation of long and very long chain fatty acyl-CoA derivatives occurs in peroxisomes, which are ubiquitous subcellular organelles of eukaryotic cells. This pathway releases acetyl-CoA as precursor for several key molecules such as cholesterol. Numerous enzymes participating to cholesterol and fatty acids biosynthesis pathways are co-localized in peroxisomes and some of their encoding genes are known as targets of the NFY transcriptional regulator. However, until now no interaction between NFY transcription factor and genes encoding peroxisomal β-oxidation has been reported. Results This work studied the interactions between NFY factor with the rat gene promoters of t…

Gene Regulation of Peroxisomal Enzymes by Nutrients, Hormones and Nuclear Signalling Factors in Animal and Human Species

Many peroxisomal enzymes are controlled at the transcriptional level. This gene regulation is well documented in liver from rodent species and is more important upon peroxisome proliferation, although both phenomena are not always associated. Understanding of this regulation comes largely from studies on PPARs (Peroxisome Proliferator-Activated Receptors). Other transcription factors including thyroid hormone receptors, glucocorticoid receptors, LXR, also influence peroxisomal gene expression often in combination with tissue specific cofactors (co-activators or co-repressors). In human tissues and cells, inducibility of peroxisomal enzymes often has not been investigated. De Craemer (1995) …

β-oxidation of long and very long chain fatty acyl-CoA derivatives occurs in peroxisomes, which are ubiquitous subcellular organelles of eukaryotic cells. This pathway releases acetyl-CoA as precursor for several key molecules such as cholesterol. Numerous enzymes participating to cholesterol and fatty acids biosynthesis pathways are co-localized in peroxisomes and some of their encoding genes are known as targets of the NFY transcriptional regulator. However, until now no interaction between NFY transcription factor and genes encoding peroxisomal β-oxidation has been reported. This work studied the interactions between NFY factor with the rat gene promoters of two enzymes of the fatty acid…

Peroxisome-proliferator-activated receptors as physiological sensors of fatty acid metabolism: molecular regulation in peroxisomes

The enzymes required for the beta-oxidation of fatty acyl-CoA are present in peroxisomes and mitochondria. Administration of hypolipidaemic compounds such as clofibrate to rodents leads to an increase in the volume and density of peroxisomes in liver cells. These proliferators also induce simultaneously the expression of genes encoding acyl-CoA oxidase, enoyl-CoA hydratase-hydroxyacyl-CoA dehydrogenase (multifunctional enzyme) and thiolase (3-ketoacyl-CoA thiolase). All these enzymes are responsible for long-chain and very-long-chain fatty acid beta-oxidation in peroxisomes. Similar results were observed when rat hepatocytes, or liver-derived cell lines, were cultured with a peroxisome prol…