PPARγ AND ERα ARE NUCLEAR RECEPTORS TARGETS OF TBBPA, BPA AND RELATED HALOGENATED COMPOUNDS
Tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) are halogenated analogues of the model xeno-estrogen bisphenol A (BPA). In this study, we used bioluminescent cell lines transfected either with human estrogen receptors (HELN-ERs) or with human PPARs (HELN-PPARs), to investigate the respective estrogenic potencies and peroxysome proliferator-activated receptors (PPARs) activities of BPA, TCBPA, TBBPA, and other brominated BPAs (mono-, di-, and tri-bromo-BPA). The agonistic activity of these compounds towards human ER and PPARγ were shown to depend upon their halogenated degree. Brominated BPAs with the highest degree of bromination exhibited the lowest estrogenic potency. Conversely, BPAs with the highest degree of halogenation had the highest potency to activate PPARγ (EC50 values of 1 μM for TBPPA and TCBPA, respectively), while no agonistic activity was observed using HELN-PPARα or PPARδ. As expected, similar results were obtained using nuclear receptors-ligand binding domain (NR-LBD) based affinity columns (recombinant human ERα-LBD, aa 302-552, or native human PPARγ-LBD, aa 205-475). The higher the degree of BPA bromination, the greater the observed retention of tested compounds on PPARγ affinity columns, and the lower their retention on ERα-based columns. hERα-LBD columns, as well as native human PPARγ-LBD based affinity columns were able to capture both high and low affinity standard ligands. In addition, PPARγ-LBD affinity columns allowed to characterise new PPARγ ligands formed following in vitro biotransformation of TBBPA. These results suggest that this BFR, but also some of its in vitro biotransformation products, may be involved in the onset of NR-triggered effects on endocrine homeostasis.
Riu A Grimaldi M Perdu-Durand E Balaguer P Zalko D
UMR 1089 Xénobiotiques,INRA-ENVT,BPF3,F-31931 Toulouse cedex 9,France INSERM U896,F-34090 Montpellier,France
国际会议
北京
英文
1-6
2009-08-24（万方平台首次上网日期，不代表论文的发表时间）