title: Copper-induced tight junction mRNA expression changes, apoptosis and antioxidant responses via NF-κB, TOR and Nrf2 signaling molecules in the gills of fish: preventive role of arginine.
abstract: This study explored the possible preventive effects of dietary arginine on copper (Cu)-induced tight junction mRNA expression changes, apoptosis and antioxidant responses in the gills of young grass carp (Ctenopharyngodon idella). The results indicated that exposure to 0.7 mg/L (11.01 μmol/L) Cu for 96 h induced the production of reactive oxygen species (ROS), thereby increasing protein oxidation, lipid peroxidation and DNA damage in the gills of fish. However, these oxidative effects were prevented by arginine supplementation. Arginine also prevented the toxic effects of Cu on the activities of copper/zinc superoxide dismutase (SOD1), glutathione-S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) and the glutathione (GSH) content (P<0.05). However, Cu induced an adaptive increase in the activity of catalase (CAT), and arginine supplementation further increased CAT activity (P<0.05). Moreover, Cu induced increases in the relative mRNA expressions of SOD1, CAT, GPx, GST, caspase-3, caspase-9, NF-E2-related factor 2 (Nrf2), Kelch-like-ECH-associated protein 1a (Keap1a), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-8 (IL-8), transforming growth factor-β (TGF-β) and nuclear transcription factor-κB p65 (NF-κB p65) in the gills of grass carp (P<0.05). In contrast, the relative mRNA expression levels of occludin, zonula occludens-1 (ZO-1), claudin b, claudin 3, claudin 12, target of rapamycin (TOR) and inhibitor factor κBα (IκBα) in the gills were decreased by Cu (P<0.05). However, pre-treatment of fish with arginine prevented Cu-induced relative mRNA expression decrease. Interestingly, Cu exposure resulted in increases in claudin 15a mRNA expression (P<0.05) but could not induce claudin c, caspase-8 and interleukin-10 (IL-10) mRNA expression changes in the gill of fish (P>0.05). These results indicated that Cu exposure induced apoptosis and antioxidant system and tight junction mRNA changes in the fish gills, which could be completely blocked by dietary arginine pre-supplementation.
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Wang
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Feng
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
authors.forename: Wei-Dan
authors.initials: WD
authors.lastname: Jiang
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Wu
authors.affiliation: Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, Sichuan, China.
authors.forename: Sheng-Yao
authors.initials: SY
authors.lastname: Kuang
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, Sichuan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Tang
authors.affiliation: Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, Sichuan, China.
authors.forename: Wu-Neng
authors.initials: WN
authors.lastname: Tang
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors.forename: Yong-An
authors.initials: YA
authors.lastname: Zhang
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan, China. Electronic address: kyckgk@hotmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan, China. Electronic address: xqzhouqq@tom.com.
authors.forename: Xiao-Qiu
authors.initials: XQ
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001120:Arginine / Q000494:pharmacology*; D002347:Carps / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003300:Copper / Q000633:toxicity*; D004032:Diet; D004789:Enzyme Activation / Q000187:drug effects; D029941:Fish Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005880:Gills / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: D029941:Fish Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014874:Water Pollutants, Chemical; D003300:Copper; D001120:Arginine; D010088:Oxidoreductases; D058570:TOR Serine-Threonine Kinases
keywords: Apoptosis; Arginine.; Copper; Gill; Signaling molecule; Tight junction