Human Peroxisomal 3-Ketoacyl-CoA Thiolase: Tissue Expression and Metabolic Regulation : Human Peroxisomal Thiolase.

Abstract

This paper reports that the human peroxisomal 3-ketoacyl-CoA thiolase expression shows three transcripts: Tr1 (1705bp), Tr2 (1375bp) and Tr3 (1782bp). Their highest expression is observed in the human liver and at a lesser extent in hepatic-derived HepG2 cells. The intestine and blood and endothelial cells show lower expression. The lowest expression is found in adipocytes. The transcript Tr3 appears to be the most abundant. So far, no data have been published regarding the regulation of the human peroxisomal thiolase. After cloning a fragment of the 5' region involved in the regulation of the human thiolase gene, the effects of different treatments have been studied on the thiolase expression in the hepatoma HepG2 human cell line. Biocomputing analysis indicates that (i) a GRE (glucocorticoid response element) is located at -650bp upstream of the transcription initiation site; (ii) a C/EBPα (CCAAT/enhancer-binding protein) binding site is located at - 1000bp upstream of the transcription initiation site - and (iii) there is no putative PPRE (peroxisome proliferator-activated receptor response element). In the human HepG2 cells, thiolase expression is upregulated by glucose and downregulated by insulin and sterols, while dexamethasone and fatty acids have no effect. The ciprofibrate, a peroxisome proliferator, leads only to a weak stimulation of the mRNA expression as compared to thiolase B expression in the rat liver.