Evolutionary Exploitation of Vertebrate Peroxisome Proliferator-Activated Receptor gamma by Organotins

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Capitao, AMF (Author) Other; Lopes Marques, MS (Author) Other; Ishii, Y (Author) Other; Ruivo, R (Author) Other; Fonseca, ESS (Author) Other; Pascoa, I (Author) Other; Jorge, RP (Author) Other; Barbosa, MAG (Author) Other; Hiromori, Y (Author) Other; Miyagi, T (Author) Other; Nakanishi, T (Author) Other; Santos, MM (Author) FCUP; Filipe F C Castro (Author) FCUP

Journal

Title: Environmental Science & Technology

Vol. 52

ISSN: 0013-936X

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 26 Citations

Scopus - 27 Citations

Other information

Authenticus ID: P-00Q-04C

DOI: 10.1021/acs.est.8b04399

Abstract (EN): Globally persistent man-made chemicals display ever-growing ecosystemic consequences, a hallmark of the Anthropocene epoch. In this context, the assessment of how lineage-specific gene repertoires influence organism sensitivity toward endocrine disruptors is a central question in toxicology. A striking example highlights the role of a group of compounds known as obesogens. In mammals, most examples involve the modulation of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR gamma). To address the structural and biological determinants of PPARy exploitation by a model obesogen, tributyltin (TBT), in chordates, we employed comparative genomics, transactivation and ligand binding assays, homology modeling, and site-directed-mutagenesis. We show that the emergence of multiple PPARs (alpha, beta and gamma) in vertebrate ancestry coincides with the acquisition of TBT agonist affinity, as can be deduced from the conserved transactivation and binding affinity of the chondrichthyan and mammalian PPAR gamma. The amphioxus single-copy PPAR is irresponsive to TBT; as well as the investigated teleosts, this is a probable consequence of a specific mutational remodeling of the ligand binding pocket. Our findings endorse the modulatory ability of man-made chemicals and suggest an evolutionarily diverse setting, with impacts for environmental risk assessment.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9