Cross-interference of two model peroxisome proliferators in peroxisomal and estrogenic pathways in brown trout hepatocytes

• Tipo: Artigo em Revista Científica Internacional
• Data: 2017

Autores

Madureira, TV (Autor) Outra; Pinheiro, I (Autor) Outra; Malhao, F (Autor) Outra; Lopes, C (Autor) Outra; Urbatzka, R (Autor) Outra; Filipe F C Castro (Autor) FCUP; rocha, e (Autor) ICBAS

Revista

Título: Aquatic Toxicology

Vol. 187

Páginas: 153-162

ISSN: 0166-445X

Editora: Elsevier

Indexação

ISI Web of Knowledge - 8 Citações

Scopus - 7 Citações

Outras Informações

ID Authenticus: P-00M-PJM

DOI: 10.1016/j.aquatox.2017.04.001

Abstract (EN): Peroxisome proliferators cause species-specific effects, which seem to be primarily transduced by peroxisome proliferator-activated receptor alpha (PPAR alpha). Interestingly, PPAR beta has a close interrelationship with estrogenic signaling, and this latter has already been promptly activated in brown trout primary hepatocytes. Thus, and further exploring this model, we assess here the reactivity of two PPARa agonists in direct peroxisomal routes and, in parallel the cross-interferences in estrogen receptor (ER) mediated paths. To achieve these goals, three independent in vitro studies were performed using single exposures to clofibrate - CLF (50, 500 and 1000 mu M), Wy-14,643 - Wy (50 and 150 mu M), GW6471 GW (1 and 101.1 mu M), and mixtures, including PPARa agonist or antagonist plus an ER agonist or antagonist. Endpoints included gene expression analysis of peroxisome/lipidic related genes (encoding apolipoprotein AI - ApoAI, fatty acid binding protein 1 - Fabp1, catalase - Cat, 17 beta-hydroxysteroid dehydrogenase 4 - 17 beta-HSD4, peroxin 11 alpha - Pexll alpha, PPAR alpha Bb, PPAR alpha Ba and urate oxidase - Uox) and those encoding estrogenic targets (ER alpha, ER beta-1 and vitellogenin A VtgA). A quantitative morphological approach by using a pre-validated catalase immunofluorescence technique allowed checking possible changes in peroxisomes. Our results show a low responsiveness of trout hepatocytes to model PPAR alpha agonists in direct target receptor pathways. Additionally, we unveiled interferences in estrogenic signaling caused by Wy, leading to an up-regulation VtgA and ER alpha at 150 mu M; these effects seem counteracted with a co-exposure to an ER antagonist. The present data stress the potential of this in vitro model for further exploring the physiological/toxicological implications related with this nuclear receptor cross-regulation.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10