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鲑科鱼类中基因组特异性的PPARαB重复基因以及褐鳟雌激素调节机制的深入研究

Genome specific PPARαB duplicates in salmonids and insights into estrogenic regulation in brown trout.

作者信息

Madureira Tânia Vieira, Pinheiro Ivone, de Paula Freire Rafaelle, Rocha Eduardo, Castro Luis Filipe, Urbatzka Ralph

机构信息

CIIMAR - Interdisciplinary Centre for Marine and Environmental Research, University of Porto (U.Porto), Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4450-208 Matosinhos, Portugal; ICBAS - Institute of Biomedical Sciences Abel Salazar, Department of Microscopy, Laboratory Histology and Embryology, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.

ICBAS - Institute of Biomedical Sciences Abel Salazar, Department of Microscopy, Laboratory Histology and Embryology, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.

出版信息

Comp Biochem Physiol B Biochem Mol Biol. 2017 Jun;208-209:94-101. doi: 10.1016/j.cbpb.2017.04.005. Epub 2017 Apr 14.

Abstract

Peroxisome proliferator-activated receptors (PPARs) are key regulators of many processes in vertebrates, such as carbohydrate and lipid metabolism. PPARα, a member of the PPAR nuclear receptor gene subfamily (NR1C1), is involved in fatty acid metabolism, namely in peroxisomal β-oxidation. Two gene paralogues, pparαA and pparαB, were described in several teleost species with their origin dating back to the teleost-specific genome duplication (3R). Given the additional salmonid-specific genome duplication (4R), four genes could be theoretically anticipated for this gene subfamily. In this work, we examined the pparα gene repertoire in brown trout, Salmo trutta f. fario. Data disclosed two pparα-like sequences in brown trout. Phylogenetic analyses further revealed that the isolated genes are most likely genome pparαB duplicates, pparαBa and pparαBb, while pparαA is apparently absent in salmonids. Both genes showed a ubiquitous mRNA expression across a panel of 11 different organs. In vitro exposed primary brown trout hepatocytes strongly suggest that pparα gene paralogues are differently regulated by ethinylestradiol (EE2). PparαBb mRNA expression significantly decreased with dosage, reaching significance after exposure to 50μM EE2, while pparαBa mRNA increased, significant at 1μM EE2. The present data enhances the understanding of pparα function and evolution in teleost, and reinforces the evidence of a potential crosstalk between estrogenic and pparα signaling pathways.

摘要

过氧化物酶体增殖物激活受体(PPARs)是脊椎动物许多生理过程的关键调节因子,如碳水化合物和脂质代谢。PPARα是PPAR核受体基因亚家族(NR1C1)的成员之一,参与脂肪酸代谢,即过氧化物酶体β-氧化。在几种硬骨鱼物种中描述了两个基因旁系同源物pparαA和pparαB,它们起源于硬骨鱼特有的基因组复制(3R)。鉴于额外的鲑科鱼类特有的基因组复制(4R),理论上可以预期这个基因亚家族有四个基因。在这项研究中,我们研究了褐鳟(Salmo trutta f. fario)中的pparα基因库。数据显示褐鳟中有两个类pparα序列。系统发育分析进一步表明,分离出的基因很可能是基因组pparαB的复制体,即pparαBa和pparαBb,而鲑科鱼类中显然不存在pparαA。这两个基因在11种不同器官中均呈现普遍的mRNA表达。体外暴露的原代褐鳟肝细胞强烈表明,pparα基因旁系同源物受乙炔雌二醇(EE2)的调控方式不同。PparαBb的mRNA表达随剂量显著降低,在暴露于50μM EE2后达到显著水平,而pparαBa的mRNA表达增加,在1μM EE2时显著。目前的数据增进了对硬骨鱼中pparα功能和进化的理解,并加强了雌激素信号通路和pparα信号通路之间潜在相互作用的证据。

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