| Added by | mollevi |
|---|---|
| Last modified by | standudu |
| Group name | EquipeVC |
| Item Type | Journal Article |
| Title | Reporter cell lines to evaluate the selectivity of chemicals for human and zebrafish estrogen and peroxysome proliferator activated gamma receptors |
| Creator | Grimaldi et al. |
| Author | M. Grimaldi |
| Author | A. Boulahtouf |
| Author | V. Delfosse |
| Author | E. Thouennon |
| Author | W. Bourguet |
| Author | P. Balaguer |
| Abstract | Zebrafish is increasingly used as an animal model to study the effects of environmental nuclear receptors (NRs) ligands. As most of these compounds have only been tested on human NRs, it is necessary to measure their effects on zebrafish NRs. Estrogen receptors (ER) alpha and beta and peroxysome proliferator activated receptor (PPAR) gamma are main targets of environmental disrupting compounds (EDCs). In humans there are two distinct nuclear ERs (hERalpha and hERbeta), whereas the zebrafish genome encodes three ERs, zfERalpha, zfERbeta1, and zfERbeta2. Only one isoform of PPARgamma is expressed in both humans and zebrafish. In this review, we described reporter cell lines that we established to study the interaction of EDCs with human and zebrafish ERs and PPARgamma. Using these cell lines, we observed that zfERs are thermo-sensitive while zfPPARgamma is not. We also showed significant differences in the ability of environmental and synthetic ligands to modulate activation of zfERs and zfPPARgamma in comparison to hERs and hPPARgamma. Some environmental estrogens (bisphenol A, mycoestrogens) which are hER panagonists displayed greater potency for zfERalpha as compared to zfERbetas. hERbeta selective agonists (8betaVE2, DPN, phytoestrogens) also displayed zfERalpha selectivity. Among hERalpha selective synthetic agonists, 16alpha-LE2 was the most zfERalpha selective compound. Almost all zfPPARgamma environmental ligands (halogenated bisphenol A derivatives, phthalates, perfluorinated compounds) displayed similar affinity for human and zebrafish PPARgamma while pharmaceutical hPPARgamma agonists like thiazolidones are not recognized by zfPPARgamma. Altogether, our studies show that all hERs and hPPARgamma ligands do not control in a similar manner the transcriptional activity of zfERs and zfPPARgamma and point out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology. |
| Publication | Front Neurosci |
| Volume | 9 |
| Pages | 212 |
| Date | 2015 |
| Journal Abbr | Frontiers in neuroscience |
| DOI | 10.3389/fnins.2015.00212 |
| ISSN | 1662-4548 (Print) 1662-453X (Linking) |
| Extra | 00000 |
| Tags | review |
| Date Added | 2018/11/14 - 12:10:52 |
| Date Modified | 2019/06/06 - 22:43:28 |
| Notes and Attachments | (Note) (Note) 26106289 (Attachment) |
Institut de Recherche en Cancérologie de
