Mixed-ligand copper(II) complexes activate aryl hydrocarbon receptor AhR and induce CYP1A genes expression in human hepatocytes and human cell lines
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
27180721
DOI
10.1016/j.toxlet.2016.05.014
PII: S0378-4274(16)30111-4
Knihovny.cz E-resources
- Keywords
- Copper(II) complexes, Cytochrome P450, Human hepatocytes, Nuclear receptors, Xenobiotics,
- MeSH
- Transcriptional Activation drug effects MeSH
- Cytochrome P-450 CYP1A1 biosynthesis genetics MeSH
- Cytochrome P-450 CYP1A2 biosynthesis genetics MeSH
- Adult MeSH
- Nitrates toxicity MeSH
- Enzyme Induction MeSH
- Phenanthrolines toxicity MeSH
- Transcription, Genetic drug effects MeSH
- Hepatocytes drug effects enzymology MeSH
- Middle Aged MeSH
- Humans MeSH
- Ligands MeSH
- Copper toxicity MeSH
- RNA, Messenger biosynthesis genetics MeSH
- MCF-7 Cells MeSH
- Primary Cell Culture MeSH
- Receptors, Aryl Hydrocarbon agonists genetics metabolism MeSH
- Aged MeSH
- Transfection MeSH
- Basic Helix-Loop-Helix Transcription Factors agonists genetics metabolism MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- 1,10-phenanthroline MeSH Browser
- AHR protein, human MeSH Browser
- copper(II) nitrate MeSH Browser
- CYP1A1 protein, human MeSH Browser
- CYP1A2 protein, human MeSH Browser
- Cytochrome P-450 CYP1A1 MeSH
- Cytochrome P-450 CYP1A2 MeSH
- Nitrates MeSH
- Phenanthrolines MeSH
- Ligands MeSH
- Copper MeSH
- RNA, Messenger MeSH
- Receptors, Aryl Hydrocarbon MeSH
- Basic Helix-Loop-Helix Transcription Factors MeSH
The effects of four copper(II) mixed-ligand complexes [Cu(qui1)(L)]NO3·H2O (1-3) and [Cu(qui2)(phen)]NO3 (4), where qui1=2-phenyl-3-hydroxy-4(1H)-quinolinone, Hqui2=2-(4-amino-3,5-dichlorophenyl)-N-propyl-3-hydroxy-4(1H)-quinolinone-7-carboxamide, L=1,10-phenanthroline (phen) (1), 5-methyl-1,10-phenanthroline (mphen) (2), bathophenanthroline (bphen) (3), on transcriptional activities of steroid receptors, nuclear receptors and xenoreceptors have been studied. The complexes (1-4) did not influence basal or ligand-inducible activities of glucocorticoid receptor, androgen receptor, thyroid receptor, pregnane X receptor and vitamin D receptor, as revealed by gene reporter assays. The complexes 1 and 2 dose-dependently induced luciferase activity in stable gene reporter AZ-AhR cell line, and this induction was reverted by resveratrol, indicating involvement of aryl hydrocarbon receptor (AhR) in the process. The complexes 1, 2 and 3 induced CYP1A1 mRNA in LS180 cells and CYP1A1/CYP1A2 in human hepatocytes through AhR. Electrophoretic mobility shift assay EMSA showed that the complexes 1 and 2 transformed AhR in its DNA-binding form. Collectively, we demonstrate that the complexes 1 and 2 activate AhR and induce AhR-dependent genes in human hepatocytes and cancer cell lines. In conclusion, the data presented here might be of toxicological importance, regarding the multiple roles of AhR in human physiology and pathophysiology.
References provided by Crossref.org
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