6533b856fe1ef96bd12b2f13

RESEARCH PRODUCT

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

subject

description

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) reviewed peroxisome proliferation in human liver diseases caused by a large variety of drugs, metabolites, infectious agents or malignancies. Duclos et al (1997) and many others found that isolated human liver cells are almost resistant to classical peroxisome proliferators (fibrates). Overexpression of mouse PPARa in human cells does not affect expression of peroxisomal fatty acid P-oxidation enzymes while, in these circumstances, the mitochondrial counterpart is subject to regulation (Hsu et al., 2001; Lawrence et al., 2001). Indeed, PPARa activates human muscle carnitine palmitoyl transferase I-CPT I (Mascaro et al 1999). On the other hand, PPAR agonists have been shown to repress human cytochrome CYP4F2-LTB4 ω-hydroxylase promoter (Zhang et al. 2000).