Basic-alimentary tractEvidence for a new human CYP1A1 regulation pathway involving PPAR-α and 2 PPRE sites
Section snippets
Chemicals
WY-14643 was purchased from VWR (Fontenay-sous-Bois, France); 2,4-TZD, 3-methylcholanthrene (3-MC), CF, BZF, and dimethyl sulfoxide were purchased from Sigma (France); and MEHP was purchased from TCI Europe (Antwerp, Belgium).
Cell culture and treatments
Human colic adenocarcinoma CaCo-2, hepatoma HepG2, and adenocarcinoma A549 cells and the primoculture of human keratinocytes were used. As soon as the CaCo-2 cells reached confluence, the culture medium was changed, and 24 hours later, they were further treated for 6 hours
Induction of the cytochrome P450 1A1 gene by peroxisome proliferator—activated receptor ligands
CaCo-2 cells were treated for 6 hours with increasing concentrations of WY-14643 (10–400 μmol/L), 50 μmol/L BZF, 50 μmol/L CF, 100 μmol/L MEHP, 200 μmol/L TZD, or 1 μmol/L 3-MC. CYP1A1 mRNA was then evaluated by quantitative real-time PCR analysis. The results presented in Figure 1A show that TZD does not increase and even decreases CYP1A1 gene expression. In contrast, CYP1A1 mRNA levels increased after treatment with the PPAR-α ligands, such as WY-14643, BZF, CF, or MEHP. The WY-14643
Discussion
We characterized a new CYP1A1 regulation pathway that involves the binding of PPAR-α transcription factor on 2 PPRE sequences located within the 5′ untranslated region of the CYP1A1 gene. The effects of agonists of PPAR-α (WY-14643, CF, BZF, and MEHP) and PPAR-γ (TZD) on CYP1A1 mRNA expression levels were evaluated in the CaCo-2 cell line by real-time quantitative real-time PCR analysis. WY-14643 induced CYP1A1 mRNA in a dose-dependent manner up to 6-fold from 200 μmol/L. Similarly, CYP1A1 mRNA
References (28)
- et al.
Regulation of cytochrome P450 enzymes by aryl hydrocarbon receptor in human cellsCYP1A2 expression in the LS180 colon carcinoma cell line after treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin or 3-methylcholanthrene
Biochem Pharmacol
(1998) - et al.
Regulation of dioxin receptor function by omeprazole
J Biol Chem
(1997) - et al.
Carbaryl induces CYP1A1 gene expression in HepG2 and HaCaT cells but is not a ligand of the human hepatic Ah receptor
Toxicol Appl Pharmacol
(1997) - et al.
Presence of a retinoid responsive element in the promoter region of the human cytochrome P4501A1 gene
Biochem Biophys Res Commun
(1994) - et al.
Shear stress increases inositol trisphosphate levels in human endothelial cells
Biochem Biophys Res Commun
(1990) - et al.
Peroxisome proliferators increase the formation of BPDE-DNA adducts in isolated rat hepatocytes
Toxicology
(1997) - et al.
Dual activation of PPARalpha and PPARgamma by mono-(2-ethylhexyl) phthalate in rat ovarian granulosa cells
Mol Cell Endocrinol
(2003) - et al.
Ethoxy-, pentoxy- and benzyloxyphenoxazones and homologuesa series of substrates to distinguish between different induced cytochromes P450
Biochem Pharmacol
(1985) - et al.
Efficient analysis of cytochrome P4501A catalytic activity, porphyrins, and total proteins in chicken embryo hepatocyte cultures with a fluorescence plate reader
Anal Biochem
(1995) - et al.
PPARalpha and PPARdelta activators inhibit cytokine-induced nuclear translocation of NF-kappaB and expression of VCAM-1 in EAhy926 endothelial cells
Eur J Pharmacol
(2002)
Transcription coactivator PBP, the peroxisome proliferator-activated receptor (PPAR)-binding protein, is required for PPARalpha-regulated gene expression in liver
J Biol Chem
Nuclear retinoid receptors and the transcription of retinoid-target genes
Gene
Metabolism of chemical carcinogens
Carcinogenesis
Alteration of pulmonary cytochrome p-450 systemeffects of asphalt fume condensate exposure
J Toxicol Environ Health
Cited by (79)
The physiology of bilirubin: health and disease equilibrium
2023, Trends in Molecular MedicineAdverse Effects of Chrysene on Human Hepatocytes via Inducement of Oxidative Stress and Dysregulation of Xenobiotic Metabolism
2023, Polycyclic Aromatic CompoundsPrenatal exposure to the phthalate DEHP impacts reproduction-related gene expression in the pituitary
2022, Reproductive ToxicologyGenetically engineered mouse models of esophageal cancer
2021, Experimental Cell ResearchCitation Excerpt :The K19 promoter is led to development and differentiation of the GI trace epithelium in both adults and embryos [76]. The Cytochrome P450 CYP1A1 gene, as a hemoprotein involved in the metabolism and synthesis of lipids, is expressed in a wide range of mouse and human tissues, which its overexpression is related to different cancer development [77]. A tissue-specific aryl hydrocarbon (Ah) receptor has been located downstream of the CYP1A1 gene to regulate its expression [70,78].
This work was a part of a multicentric study under the authority of Dr. A. Sasco (International Agency for Research on Cancer/Institut National de la Santé et de la Recherche Médicale [INSERM]) and was partly funded by Ligue Nationale contre le Cancer, Comité du Rhône, Association de Recherche sur le Cancer (research project 3410), and INSERM (Action Thématique Concertée Environnement et Santé, Grant ASE 02048SSP).
- 1
E.S. and P.-H.V. contributed equally to this work.