Endoplasmic reticulum stress and disturbed calcium homeostasis are involved in copper-induced alteration in hepatic lipid metabolism in yellow catfish Pelteobagrus fulvidraco. (February 2016)

• Record Type: Journal Article
• Authors: Song, Yu-Feng; Luo, Zhi; Zhang, Li-Han; Hogstrand, Christer; Pan, Ya-Xiong
• Is Part Of: Chemosphere. Volume 144(2016)
• Page Start: 2443
• Page End: 2453
• Publication Date: 2016-02
• Subjects: Pelteobagrus fulvidraco -- Copper -- Endoplasmic reticulum stress -- Calcium homeostasis -- Lipid metabolism; DMSO dimethyl sulfoxide -- MS-222 tricaine methanesulfonate -- M199 Medium 199 -- FBS fetal bovine serum -- PBS phosphate buffered saline -- TG triglyceride -- PPAR peroxisome proliferators-activated receptor -- SREBP-1 sterol-regulator element-binding protein-1 -- LXR Liver X receptor -- ACC acetyl-CoA carboxylase -- FAS fatty acid synthase -- SCD stearoyl-coA desaturase -- GRP78/BiP 78-kDa glucose-regulated protein -- GRP94 94-kDa glucose-regulated protein -- CRT calreticulin -- PERK protein kinase RNA-activated-like ER kinase -- eIF2α eukaryotic translation initiation factor 2 alpha -- IRE1 inositol-requiring enzyme 1 -- XBP1 X-box binding protein 1 -- ATF6 activating transcription factor 6 -- IP3 inositol 1 -- 4 5-trisphosphate -- RyR ryanodine receptor; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2015.11.031
• Languages: English
• ISSNs: 0045-6535

Abstract

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. Highlights: ER stress contributes to lipid accumulation in Cu-evoked change of lipid metabolism. The release of Ca 2+ from the ER contributed to dysregulation of lipid metabolism. Cu-induced alteration in lipid metabolism was suppressed through the attenuation of ER stress.