ArticleChemical research in toxicology2011
The p38 MAPK inhibitor SB203580 induces cytochrome P450 1A1 gene expression in murine and human hepatoma cell lines through ligand-dependent aryl hydrocarbon receptor activation.
Article in Chemical research in toxicology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 32 citations in OpenAlex.
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- Activation of the aryl hydrocarbon receptor by clozapine induces preadipocyte differentiation and contributes to endothelial dysfunction.Journal of psychopharmacology (Oxford, England) · 2022Article
- Vemurafenib acts as an aryl hydrocarbon receptor antagonist: Implications for inflammatory cutaneous adverse events.Allergy · 2019Article
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- Commentary: Usage of Mitogen-Activated Protein Kinase Small Molecule Inhibitors: More Than Just Inhibition!Frontiers in pharmacology · 2018Article
- Chenodeoxycholic acid increases the induction of CYP1A1 in HepG2 and H4IIE cells.Experimental and therapeutic medicine · 2015Article
- Activation of the aryl hydrocarbon receptor by the widely used Src family kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine (PP2).Archives of toxicology · 2015Article
- Pityriazepin and other potent AhR ligands isolated from Malassezia furfur yeast.Archives of biochemistry and biophysics · 2015Article
- Effects of anthocyanins on the AhR-CYP1A1 signaling pathway in human hepatocytes and human cancer cell lines.Toxicology letters · 2013Article
- Pelargonidin activates the AhR and induces CYP1A1 in primary human hepatocytes and human cancer cell lines HepG2 and LS174T.Toxicology letters · 2013Article
- Camel milk triggers apoptotic signaling pathways in human hepatoma HepG2 and breast cancer MCF7 cell lines through transcriptional mechanism.Journal of biomedicine & biotechnology · 2012Article
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Authors and funding
5 authors at 3 institutions in 3 countries.
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Abstract
We have previously shown that the p38 MAPK inhibitor SB203580 (SB) significantly induced Cyp1a1 gene expression at the mRNA and activity levels, whereas it dramatically inhibited the induction of Cyp1a1 by TCDD in murine hepatoma Hepa 1c1c7 cells. However, the molecular mechanisms involved were not investigated yet. Therefore, the current study aims to examine the capacity of SB to induce the constitutive CYP1A1 gene expression in Hepa 1c1c7 and HepG2 cells and to explore the mechanisms involved. Our results showed that SB induced the Cyp1a1 mRNA, protein, and activity levels in a concentration-dependent manner in Hepa 1c1c7 cells. The increase in Cyp1a1 mRNA by SB was completely blocked by the transcriptional inhibitor, actinomycin D, implying that SB increased de novo RNA synthesis. In addition, the lack of Cyp1a1 induction by SB in mutant aryl hydrocarbon receptor (AhR)-deficient C12 cells and with cotreatment with the AhR antagonist, α-naphthoflavone, clearly suggests an AhR-dependent induction. This was further supported by the ability of SB to induce Cyp1a1 independent from its effect on MAPKs, and to bind to and activate AhR transformation and its subsequent binding to the xenobiotic responsive element (XRE). This is the first demonstration that the p38 MAPK inhibitor, SB can directly bind to and activate AhR-induced Cyp1a1 gene expression in an AhR-dependent manner and represents a novel mechanism by which SB induces this enzyme.
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