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稀有鮈鲫(Gobiocypris rarus)鳃中细胞色素P450 1A和3A的分子特征及全氟辛酸对其mRNA水平的影响

Molecular characterization of cytochrome P450 1A and 3A and the effects of perfluorooctanoic acid on their mRNA levels in rare minnow (Gobiocypris rarus) gills.

作者信息

Liu Yong, Wang Jianshe, Wei Yanhong, Zhang Hongxia, Liu Yang, Dai Jiayin

机构信息

Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, PR China.

出版信息

Aquat Toxicol. 2008 Jul 7;88(3):183-90. doi: 10.1016/j.aquatox.2008.04.008. Epub 2008 Apr 22.

DOI:10.1016/j.aquatox.2008.04.008
PMID:18508136
Abstract

Perfluorooctanoic acid (PFOA), a potentially toxic perfluorinated compound (PFC), has been widely disseminated in the environment. In the present study, rare minnows (Gobiocypris rarus) exposed to PFOA exhibited histopathological gill damage, including epithelial hyperplasia of the lamellae, inflammatory cell infiltration, and lamellar fusion. Cytochrome P450s (CYPs) play a central role in the metabolism and biotransformation of a wide range of endogenous substrates and foreign compounds. Thus, we studied the CYPs and the effects of waterborne PFOA on their corresponding mRNA levels in the gills of rare minnows. Two novel CYP cDNAs (CYP1A and CYP3A) were identified in rare minnow and their mRNAs were ubiquitously expressed in all tissues examined. Upregulation of CYP3A mRNA was observed in the gills of male rare minnows exposed to 30mg/L PFOA, while no significant changes occurred in exposed females. In contrast, down regulation of CYP1A mRNA was detected in the gills of male and female minnows exposed to PFOA. However, the effect of PFOA on gill mRNA levels of their potential regulators, aryl hydrocarbon receptor (AhR) for CYP1A, and pregnane X receptor (PXR) for CYP3A, were not consistent with the observed effects of PFOA on the corresponding CYP mRNA concentrations. This suggests a different or more complex transcriptional regulation of CYP expression following PFOA exposure.

摘要

全氟辛酸(PFOA)是一种具有潜在毒性的全氟化合物(PFC),已在环境中广泛传播。在本研究中,暴露于PFOA的稀有鮈鲫表现出鳃组织病理学损伤,包括鳃小片上皮增生、炎性细胞浸润和鳃小片融合。细胞色素P450(CYPs)在多种内源性底物和外来化合物的代谢及生物转化中起核心作用。因此,我们研究了稀有鮈鲫鳃中的CYPs以及水环境中PFOA对其相应mRNA水平的影响。在稀有鮈鲫中鉴定出两个新的CYP cDNA(CYP1A和CYP3A),它们的mRNA在所检测的所有组织中均有广泛表达。在暴露于30mg/L PFOA的雄性稀有鮈鲫鳃中观察到CYP3A mRNA上调,而暴露的雌性中未发生显著变化。相反,在暴露于PFOA的雄性和雌性鮈鲫鳃中均检测到CYP1A mRNA下调。然而,PFOA对其潜在调节因子(CYP1A的芳烃受体(AhR)和CYP3A的孕烷X受体(PXR))鳃mRNA水平的影响与观察到的PFOA对相应CYP mRNA浓度的影响不一致。这表明PFOA暴露后CYP表达存在不同或更复杂的转录调控。

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