title: Endoplasmic reticulum stress and disturbed calcium homeostasis are involved in copper-induced alteration in hepatic lipid metabolism in yellow catfish Pelteobagrus fulvidraco.
abstract: The present study was conducted to investigate the effect of Cu exposure on ER stress and Ca(2+) homeostasis, and explore the underlying mechanism of the ER stress and disturbed Ca(2+) homeostasis in the regulation of hepatic lipid metabolism in yellow catfish Pelteobagrus fulvidraco. To this end, three experiments were conducted. In experiment 1, P. fulvidraco were exposed to three waterborne Cu concentrations for 56 days. Waterborne Cu exposure evoked ER stress and SREBP-1c activation and resulted in dysregulation of hepatic lipid metabolism in liver of P. fulvidraco in a time-dependent manner. In experiment 2, specific inhibitors 2-APB (IP3 receptor inhibitor) and dantrolene (RyR receptor inhibitor) were used to explore whether Ca(2+) release from ER was involved in the Cu-induced ER stress change. Dantrolene and 2-APB prevented Cu-induced intracellular Ca(2+) elevation, demonstrating that the release of Ca(2+) from the ER, mediated by both RyR and IP3R, contributed to dysregulation of lipid metabolism. In experiment 3, a chemical chaperone (PBA) was used to demonstrate whether Cu-induced alteration in lipid metabolism was suppressed through the attenuation of ER stress. PBA attenuated the Cu-induced elevation of mRNA expression of SREBP-1c, SCAP, ACC, FAS, GRP78/BiP, GRP94, CRT, eIF2α and XBP-1, and alleviated the Cu-induced downregulation of Insig-1. Based on these observations, these results reveal a link between ER stress and the change of lipid metabolism induced by Cu, which will help to understand the Cu-induced toxicity on cellular and molecular level, and provide some novel insights into the regulation of lipid metabolism in fish.
authors.affiliation: Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University, Wuhan, 430070, PR China; China and Freshwater Aquaculture Collaborative Innovative Center of Hubei Province, Wuhan, 430070, PR China.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Song
authors.affiliation: Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University, Wuhan, 430070, PR China; China and Freshwater Aquaculture Collaborative Innovative Center of Hubei Province, Wuhan, 430070, PR China. Electronic address: luozhi99@mail.hzau.edu.cn.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University, Wuhan, 430070, PR China; China and Freshwater Aquaculture Collaborative Innovative Center of Hubei Province, Wuhan, 430070, PR China.
authors.forename: Li-Han
authors.initials: LH
authors.lastname: Zhang
authors.affiliation: Diabetes and Nutritional Sciences Division, School of Medicine, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
authors.forename: Christer
authors.initials: C
authors.lastname: Hogstrand
authors.affiliation: Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Fishery College, Huazhong Agricultural University, Wuhan, 430070, PR China; China and Freshwater Aquaculture Collaborative Innovative Center of Hubei Province, Wuhan, 430070, PR China.
authors.forename: Ya-Xiong
authors.initials: YX
authors.lastname: Pan
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D002397:Catfishes / Q000235:genetics / Q000502:physiology*; D003300:Copper / Q000633:toxicity*; D059865:Endoplasmic Reticulum Stress; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000502:physiology; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D029941:Fish Proteins; D014874:Water Pollutants, Chemical; D003300:Copper; D002118:Calcium
keywords: Calcium homeostasis; Copper; Endoplasmic reticulum stress; Lipid metabolism; Pelteobagrus fulvidraco