Abstract
This paper reports that the human peroxisomal 3-ketoacyl-CoA thiolase expression shows three transcripts: Tr1 (1705 bp), Tr2 (1375 bp) and Tr3 (1782 bp). 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 −650 bp upstream of the transcription initiation site; (ii) a C/EBPα (CCAAT/enhancer-binding protein) binding site is located at − 1000 bp 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.
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Abbreviations
- C/EBPα:
-
CCAAT/enhancer-binding protein
- Chol/25-OHC:
-
cholesterol/25-hydroxycholesterol
- GRE:
-
glucocorticoid response element
- PEX proteins:
-
peroxins
- PPAR:
-
peroxisome proliferators-activated receptor
- PPRE:
-
peroxisome proliferator-activated receptor response element
- PTS2:
-
peroxisomal targeting sequence type 2
- TAT:
-
tyrosine aminotransferase
- TH:
-
3-ketoacyl-CoA thiolase
- Tr1,2,3:
-
thiolase transcripts 1,2 or 3
- SCPx:
-
sterol carrier protein
- VLCFA:
-
very-long-chain fatty acid
- X-ALD:
-
X-linked adrenoleukodystrophy
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Acknowledgements
This work has been realized with the contribution of Prof. Norbert Latruffe’s « Thiolase » group Université de Bourgogne/Inserm U866. This group was constituted of Dr. Caroline Marmier, Dr. Catherine Le Jossic-Corcos, Dr. Valérie Nicolas, Dr. Stéphane Mandard and Dr. Ségolène Arnaud.
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Latruffe, N. (2020). Human Peroxisomal 3-Ketoacyl-CoA Thiolase: Tissue Expression and Metabolic Regulation. In: Lizard, G. (eds) Peroxisome Biology: Experimental Models, Peroxisomal Disorders and Neurological Diseases. Advances in Experimental Medicine and Biology, vol 1299. Springer, Cham. https://doi.org/10.1007/978-3-030-60204-8_12
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