| Added by | mollevi |
|---|---|
| Last modified by | standudu |
| Group name | EquipeVC |
| Item Type | Journal Article |
| Title | Skatole (3-Methylindole) Is a Partial Aryl Hydrocarbon Receptor Agonist and Induces CYP1A1/2 and CYP1B1 Expression in Primary Human Hepatocytes |
| Creator | Rasmussen et al. |
| Author | M. K. Rasmussen |
| Author | P. Balaguer |
| Author | B. Ekstrand |
| Author | M. Daujat-Chavanieu |
| Author | S. Gerbal-Chaloin |
| Abstract | Skatole (3-methylindole) is a product of bacterial fermentation of tryptophan in the intestine. A significant amount of skatole can also be inhaled during cigarette smoking. Skatole is a pulmonary toxin that induces the expression of aryl hydrocarbon receptor (AhR) regulated genes, such as cytochrome P450 1A1 (CYP1A1), in human bronchial cells. The liver has a high metabolic capacity for skatole and is the first organ encountered by the absorbed skatole; however, the effect of skatole in the liver is unknown. Therefore, we investigated the impact of skatole on hepatic AhR activity and AhR-regulated gene expression. Using reporter gene assays, we showed that skatole activates AhR and that this is accompanied by an increase of CYP1A1, CYP1A2 and CYP1B1 expression in HepG2-C3 and primary human hepatocytes. Specific AhR antagonists and siRNA-mediated AhR silencing demonstrated that skatole-induced CYP1A1 expression is dependent on AhR activation. The effect of skatole was reduced by blocking intrinsic cytochrome P450 activity and indole-3-carbinole, a known skatole metabolite, was a more potent inducer than skatole. Finally, skatole could reduce TCDD-induced CYP1A1 expression, suggesting that skatole is a partial AhR agonist. In conclusion, our findings suggest that skatole and its metabolites affect liver homeostasis by modulating the AhR pathway. |
| Publication | PLoS One |
| Volume | 11 |
| Pages | e0154629 |
| Date | 2016 |
| Journal Abbr | PloS one |
| DOI | 10.1371/journal.pone.0154629 |
| ISSN | 1932-6203 (Electronic) 1932-6203 (Linking) |
| Extra | 00000 |
| Tags | original |
| Date Added | 2018/11/14 - 12:10:52 |
| Date Modified | 2019/06/06 - 22:43:26 |
| Notes and Attachments | (Note) (Note) 27138278 (Attachment) |
Institut de Recherche en Cancérologie de
