کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1977545 1061500 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Tributyltin is a potent inhibitor of piscine peroxisome proliferator-activated receptor α and β
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Tributyltin is a potent inhibitor of piscine peroxisome proliferator-activated receptor α and β
چکیده انگلیسی

Increasing evidence suggests that common environmental contaminants can act as endocrine disrupters in fish. However, current data are biased towards environmental estrogens, highlighting the need to elucidate potential pollutant impact on other endocrine axes. Here, we report a high-throughput assay to identify chemicals interacting with piscine peroxisome proliferator-activated receptors (PPARs). Our transactivation assay employs a fish cell line and uses recombinant proteins combining the yeast Gal4 DNA-binding domain with the ligand-binding domain of PPARs from plaice (Pleuronectes platessa). Compared to assays with full-length PPARs, this approach circumvents interaction of chemicals binding to retinoid X receptors, which form heterodimers with PPAR and many other nuclear receptors. Plaice PPARα and PPARβ are activated by fibrate drugs and by phthalate mono-esters at concentrations similar to those activating the homologous mammalian receptors. In line with their assumed role as central transcriptional regulators of energy homeostasis, a number of fatty acids activate plaice PPARα and PPARβ. In contrast, tributyl tin oxide (TBTO) is a potent antagonist of PPARα and PPARβ, showing activity at environmentally relevant concentrations of TBTO (1–50 nM). Given the ubiquitous and persistent nature of TBTO, the possibility that chronic environmental effects are occurring via disruption of PPAR signalling in fish should be further investigated.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology - Volume 153, Issue 1, January 2011, Pages 168–173
نویسندگان
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