Histidine Prevents Cu-Induced Oxidative Stress and the Associated Decreases in mRNA from Encoding Tight Junction Proteins in the Intestine of Grass Carp (Ctenopharyngodon idella).
Copper (Cu) is a common heavy metal pollutant in aquatic environments that originates from natural as well as anthropogenic sources. The present study investigated whether Cu causes oxidative damage and induces changes in the expression of genes that encode tight junction (TJ) proteins, cytokines and antioxidant-related genes in the intestine of the grass carp (Ctenopharyngodon idella). We demonstrated that Cu decreases the survival rate of fish and increases oxidative damage as measured by increases in malondialdehyde and protein carbonyl contents. Cu exposure significantly decreased the expression of genes that encode the tight junction proteins, namely, claudin (CLDN)-c, -3 and -15 as well as occludin and zonula occludens-1, in the intestine of fish. In addition, Cu exposure increases the mRNA levels of the pro-inflammatory cytokines, specifically, IL-8, TNF-α and its related signalling factor (nuclear factor kappa B, NF-κB), which was partly correlated to the decreased mRNA levels of NF-κB inhibitor protein (IκB). These changes were associated with Cu-induced oxidative stress detected by corresponding decreases in glutathione (GSH) content, as well as decreases in the copper, zinc-superoxide dismutase (SOD1) and glutathione peroxidase (GPx) activities and mRNA levels, which were associated with the down-regulated antioxidant signalling factor NF-E2-related factor-2 (Nrf2) mRNA levels, and the Kelch-like-ECH-associated protein1 (Keap1) mRNA levels in the intestine of fish. Histidine supplementation in diets (3.7 up to 12.2 g/kg) blocked Cu-induced changes. These results indicated that Cu-induced decreases in intestinal TJ proteins and cytokine mRNA levels might be partially mediated by oxidative stress and are prevented by histidine supplementation in fish diet.
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.
Wei-Dan
WD
Jiang
Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.
Biao
B
Qu
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.
Lin
L
Feng
Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.
Jun
J
Jiang
Animal Nutrition Institute, Sichuan Academy of Animal Science, 610066, Chengdu, China.
Sheng-Yao
SY
Kuang
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.
Pei
P
Wu
Animal Nutrition Institute, Sichuan Academy of Animal Science, 610066, Chengdu, China.
Ling
L
Tang
Animal Nutrition Institute, Sichuan Academy of Animal Science, 610066, Chengdu, China.
Wu-Neng
WN
Tang
Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.
Yong-An
YA
Zhang
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.
Xiao-Qiu
XQ
Zhou
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.
Yang
Y
Liu
D000818:Animals; D002347:Carps / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D003300:Copper / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D029941:Fish Proteins / Q000235:genetics*; D006639:Histidine / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D015398:Signal Transduction; D062725:Tight Junction Proteins / Q000235:genetics*
D016207:Cytokines; D029941:Fish Proteins; D012333:RNA, Messenger; D062725:Tight Junction Proteins; D006639:Histidine; D003300:Copper