The Echinodermata PPAR: Functional characterization and exploitation by the model lipid homeostasis regulator tributyltin.,Environmental Pollution

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The Echinodermata PPAR: Functional characterization and exploitation by the model lipid homeostasis regulator tributyltin.
Environmental Pollution ( IF 7.6 ) Pub Date : 2020-04-01 , DOI: 10.1016/j.envpol.2020.114467
Ana Capitão ₁ , Mónica Lopes-Marques ₂ , Inês Páscoa ₂ , Raquel Ruivo ₂ , Nicolau Mendiratta ₂ , Elza Fonseca ₁ , L Filipe C Castro ₁ , Miguel Machado Santos ₁

Affiliation

The wide ecological relevance of lipid homeostasis modulators in the environment has been increasingly acknowledged. Tributyltin (TBT), for instance, was shown to cause lipid modulation, not only in mammals, but also in fish, molluscs, arthropods and rotifers. In vertebrates, TBT is known to interact with a nuclear receptor heterodimer module, formed by the retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor (PPAR). These modulate the expression of genes involved in lipid homeostasis. In the present work, we isolated for the first time the complete coding region of the Echinodermata (Paracentrotus lividus) gene orthologues of PPAR and RXR and evaluated the ability of a model lipid homeostasis modulator, TBT, to interfere with the lipid metabolism in this species. Our results demonstrate that TBT alters the gonadal fatty acid composition and gene expression patterns: yielding sex-specific responses in fatty acid levels, including the decrease of eicosapentaenoic acid (C20:5 n-3, EPA) in males, and increase of arachidonic acid (20:4n-6, ARA) in females, and upregulation of long-chain acyl-CoA synthetase (acsl), ppar and rxr. Furthermore, an in vitro test using COS-1 cells as host and chimeric receptors with the ligand binding domain (LBD) of P. lividus PPAR and RXR shows that organotins (TBT and TPT (Triphenyltin)) suppressed activity of the heterodimer PPAR/RXR in a concentration-dependent manner. Together, these results suggest that TBT acts as a lipid homeostasis modulator at environmentally relevant concentrations in Echinodermata and highlight a possible conserved mode of action via the PPAR/RXR heterodimer.

中文翻译：

Echinodermata PPAR：模型脂质稳态调节剂三丁基锡的功能表征和开发。

脂质稳态调节剂在环境中的广泛生态相关性已得到越来越多的认可。例如，三丁基锡（TBT）已显示不仅在哺乳动物中，而且在鱼类，软体动物，节肢动物和轮虫中都引起脂质调节。在脊椎动物中，已知TBT与类视黄醇X受体（RXR）和过氧化物酶体增殖物激活受体（PPAR）形成的核受体异二聚体模块相互作用。这些调节涉及脂质稳态的基因的表达。在本工作中，我们首次分离了PPAR和RXR的棘皮动物（Paracentrotus lividus）基因直向同源物的完整编码区，并评估了模型脂质稳态调节剂TBT干扰该物种脂质代谢的能力。。我们的研究结果表明，TBT改变了性腺脂肪酸的组成和基因表达模式：在脂肪酸水平上产生性别特异性反应，包括男性中二十碳五烯酸（C20：5 n-3，EPA）的减少和花生四烯酸的增加（20：4n-6，ARA）在女性中的表达，以及长链酰基辅酶A合成酶（acsl），ppar和rxr的上调。此外，使用COS-1细胞作为宿主和嵌合受体（带有青紫假单胞菌PPAR和RXR的配体结合域（LBD））的体外测试表明，有机锡（TBT和TPT（三苯基锡））抑制了异二聚体PPAR / RXR的活性以浓度依赖的方式。一起，

更新日期：2020-04-20

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