Fullerene inhibits benzo(a)pyrene Efflux from Cyprinus carpio hepatocytes by affecting cell membrane fluidity and P-glycoprotein expression
Fullerene inhibits benzo(a)pyrene Efflux from Cyprinus carpio hepatocytes by affecting cell membrane fluidity and P-glycoprotein expression
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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) 芘的流出
DOI：
10.1016/j.aquatox.2016.02.008
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发表时间：
2016-05-01
影响因子：
4.5
通讯作者：
Yin, Daqiang
中科院分区：
文献类型：
--
作者：
Chen, Qiqing;Hu, Xialin;Yin, Daqiang
P-糖蛋白(P-gp)可以通过排出有毒化合物来保护细胞，已发现在鱼类组织中广泛表达。在这里，我们阐明了在富勒烯水悬浮液(NC(60))中暴露于鲤鱼(Cyprinus Carpio)的肝细胞中，P-糖蛋白对苯并(A)芘(BaP)的外排能力。结果表明，NC(60)通过降低饱和脂肪酸与不饱和脂肪酸的比例，提高膜的流动性，增加胆固醇的含量。这些结果，再加上P-gp基因和蛋白的表达分别下调10-38%和70-75%，提示NC(60)对P-gp外流转运系统有抑制作用。因此，我们进一步研究了BaP的细胞外排能力。结果表明，NC(60)是一种有效的P-gp抑制剂。在暴露10天内，排出后的BaP滞留量增加了1.7-2.8倍。同时，5 mg/L腐植酸(天然有机物的重要组分之一，广泛存在于水环境中)可从氧化损伤、胆固醇升高和P-糖蛋白含量降低等方面减轻NC(60)对肝细胞的损伤，最终减弱抑制的P-糖蛋白外排能力。总之，这项研究首次提供了NC(60)对鱼类P-gp功能毒性的证据，并阐明了抑制P-gp对BaP的外排能力的可能机制。(C)2016爱思唯尔B.V.保留所有权利。
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 (nC(60)). The results revealed that nC(60) 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 nC(60) caused inhibition on P-gp efflux transport system. Therefore, we further investigated the cellular efflux ability for BaP. Results showed unequivocally that nC(60) 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, 5 mg/L humic acid (one of the important fractions of natural organic matter, which is ubiquitous in aquatic environment) alleviated the nC(60) 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 nC(60) toxicity to P-gp functionality in fish and illustrates the possible mechanism of the suppressed P-gp efflux ability for BaP. (C) 2016 Elsevier B.V. All rights reserved.