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富勒烯通过影响细胞膜流动性和P-糖蛋白表达来抑制鲤鱼肝细胞中苯并(a)芘的外排。

Fullerene inhibits benzo(a)pyrene Efflux from Cyprinus carpio hepatocytes by affecting cell membrane fluidity and P-glycoprotein expression.

作者信息

Chen Qiqing, Hu Xialin, Wang Rui, Yuan Jin, Yin Daqiang

机构信息

Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, 1239 Siping Road, Shanghai 200092, China; State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, 1239 Siping Road, Shanghai 200092, China.

Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, 1239 Siping Road, Shanghai 200092, China; State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, 1239 Siping Road, Shanghai 200092, China.

出版信息

Aquat Toxicol. 2016 May;174:36-45. doi: 10.1016/j.aquatox.2016.02.008. Epub 2016 Feb 19.

Abstract

P-Glycoprotein (P-gp) can protect cells by pumping out toxic compounds, and has been found widely expressed in fish tissues. Here, we illustrate the P-gp efflux ability for benzo(a)pyrene (BaP) in the hepatocytes of common carp (Cyprinus carpio) after exposing to fullerene aqueous suspension (nC60). The results revealed that nC60 increased the membrane fluidity by decreasing the ratio of saturated to unsaturated fatty acids, and increased the cholesterol contents. These findings, combined with 10-38% and 70-75% down-regulation of P-gp mRNA and protein respectively, suggested that nC60 caused inhibition on P-gp efflux transport system. Therefore, we further investigated the cellular efflux ability for BaP. Results showed unequivocally that nC60 is a potent P-gp inhibitor. The retaining BaP amounts after efflux were elevated by 1.7-2.8 fold during the 10 day exposure. Meanwhile, 5mg/L humic acid (one of the important fractions of natural organic matter, which is ubiquitous in aquatic environment) alleviated the nC60 damage to hepatocytes in terms of oxidative damage, cholesterol increment, and P-gp content reduction; and finally attenuated the suppressed P-gp efflux ability. Collectively, this study provides the first evidence of nC60 toxicity to P-gp functionality in fish and illustrates the possible mechanism of the suppressed P-gp efflux ability for BaP.

摘要

P-糖蛋白(P-gp)可通过泵出有毒化合物来保护细胞,并且已发现其在鱼类组织中广泛表达。在此,我们阐述了暴露于富勒烯水悬浮液(nC60)后,鲤鱼(Cyprinus carpio)肝细胞中P-gp对苯并(a)芘(BaP)的外排能力。结果显示,nC60通过降低饱和脂肪酸与不饱和脂肪酸的比例增加了膜流动性,并提高了胆固醇含量。这些发现,再结合P-gp mRNA和蛋白分别下调10 - 38%和70 - 75%,表明nC60对P-gp外排转运系统产生了抑制作用。因此,我们进一步研究了细胞对BaP的外排能力。结果明确表明,nC60是一种有效的P-gp抑制剂。在10天的暴露期间,外排后保留的BaP量增加了1.7 - 2.8倍。同时,5mg/L的腐殖酸(天然有机物的重要组分之一,在水生环境中普遍存在)在氧化损伤、胆固醇增加和P-gp含量降低方面减轻了nC60对肝细胞的损伤;并最终减弱了被抑制的P-gp外排能力。总体而言,本研究首次提供了nC60对鱼类P-gp功能毒性的证据,并阐明了BaP的P-gp外排能力受到抑制的可能机制。

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