Butyrate alters expression of cytochrome P450 1A1 and metabolism of benzo[a]pyrene via its histone deacetylase activity in colon epithelial cell models
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články
PubMed
27830268
DOI
10.1007/s00204-016-1887-4
PII: 10.1007/s00204-016-1887-4
Knihovny.cz E-zdroje
- Klíčová slova
- Butyrate, CYP1A1, Colon epithelial cells, DNA adducts, Histone deacetylases, Polycyclic aromatic hydrocarbons,
- MeSH
- adukty DNA účinky léků metabolismus MeSH
- benzopyren metabolismus farmakokinetika MeSH
- beta-katenin metabolismus MeSH
- buňky HT-29 MeSH
- cytochrom P-450 CYP1A1 genetika metabolismus MeSH
- HCT116 buňky MeSH
- histondeacetylasa 1 antagonisté a inhibitory metabolismus MeSH
- histony metabolismus MeSH
- inhibitory histondeacetylas farmakologie MeSH
- kolon účinky léků metabolismus MeSH
- kyselina máselná farmakologie MeSH
- lidé MeSH
- metabolická inaktivace MeSH
- zesilovače transkripce účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adukty DNA MeSH
- benzopyren MeSH
- beta-katenin MeSH
- CTNNB1 protein, human MeSH Prohlížeč
- CYP1A1 protein, human MeSH Prohlížeč
- cytochrom P-450 CYP1A1 MeSH
- HDAC1 protein, human MeSH Prohlížeč
- histondeacetylasa 1 MeSH
- histony MeSH
- inhibitory histondeacetylas MeSH
- kyselina máselná MeSH
Butyrate, a short-chain fatty acid produced by fermentation of dietary fiber, is an important regulator of colonic epithelium homeostasis. In this study, we investigated the impact of this histone deacetylase (HDAC) inhibitor on expression/activity of cytochrome P450 family 1 (CYP1) and on metabolism of carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP), in colon epithelial cells. Sodium butyrate (NaBt) strongly potentiated the BaP-induced expression of CYP1A1 in human colon carcinoma HCT116 cells. It also co-stimulated the 7-ethoxyresorufin-O-deethylase (EROD) activity induced by the 2,3,7,8-tetrachlorodibenzo-p-dioxin, a prototypical ligand of the aryl hydrocarbon receptor. Up-regulation of CYP1A1 expression/activity corresponded with an enhanced metabolism of BaP and formation of covalent DNA adducts. NaBt significantly potentiated CYP1A1 induction and/or metabolic activation of BaP also in other human colon cell models, colon adenoma AA/C1 cells, colon carcinoma HT-29 cells, or in NCM460D cell line derived from normal colon mucosa. Our results suggest that the effects of NaBt were due to its impact on histone acetylation, because additional HDAC inhibitors (trichostatin A and suberanilohydroxamic acid) likewise increased both the induction of EROD activity and formation of covalent DNA adducts. NaBt-induced acetylation of histone H3 (at Lys14) and histone H4 (at Lys16), two histone modifications modulated during activation of CYP1A1 transcription, and it reduced binding of HDAC1 to the enhancer region of CYP1A1 gene. This in vitro study suggests that butyrate, through modulation of histone acetylation, may potentiate induction of CYP1A1 expression, which might in turn alter the metabolism of BaP within colon epithelial cells.
Department of Chemistry and Toxicology Veterinary Research Institute 62100 Brno Czech Republic
Department of Experimental Biology Faculty of Science Masaryk University 61137 Brno Czech Republic
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