title: Fullerene inhibits benzo(a)pyrene Efflux from Cyprinus carpio hepatocytes by affecting cell membrane fluidity and P-glycoprotein expression.
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.
authors.affiliation: 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.
authors.forename: Qiqing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Xialin
authors.initials: X
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Jin
authors.initials: J
authors.lastname: Yuan
authors.affiliation: 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. Electronic address: yindq@tongji.edu.cn.
authors.forename: Daqiang
authors.initials: D
authors.lastname: Yin
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D002347:Carps / Q000378:metabolism*; D037741:Fullerenes / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects*; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D037741:Fullerenes; D014874:Water Pollutants, Chemical; D001564:Benzo(a)pyrene
keywords: Benzo(a)pyrene; Cell membrane; Cyprinus carpio; Efflux ability; Fullerene; P-Glycoprotein