title: Microcystin-LR altered mRNA and protein expression of endoplasmic reticulum stress signaling molecules related to hepatic lipid metabolism abnormalities in mice.
abstract: To explore the effects of microcystin-LR (MC-LR), a hepatotoxin, on the incidence of liver lipid metabolism abnormality, and the potential molecular mechanisms of action, healthy male Balb/c mice were intraperitoneally injected with MC-LR at doses of 0, 5, 10, and 20 μg/kg/d for 14 days. Hepatic histopathology and serum lipid parameters of mice were determined, and the changes of mRNA and protein expression of endoplasmic reticulum (ER) stress signaling molecules related to the lipid metabolism abnormalities in the livers of mice were investigated by quantitative real-time polymerase chain reaction (qPCR) and Western blotting, respectively. The results indicated that 5-20 μg/kg/d MC-LR altered serum lipid parameters and caused hepatic steatosis. MC-LR treatment at 10 or 20 μg/kg/d changed mRNA and protein expression of ER stress signaling molecules, including upregulation of mRNA and protein expression of activating transcription factor 6 (ATF6), pancreatic ER eukaryotic translation initiation factor 2α (eIF-2α) kinase (PERK), and eIF-2α. MC-LR exposure at 10 or 20 μg/kg/d also altered mRNA and protein expression of downstream factors and genes of ER stress signaling pathways, including the downregulation of sterol regulatory element binding protein 1c (SREBP-1c) and fatty acid synthase (FASn), and upregulation of acetyl-coenzyme A carboxylase α (ACACA) and glycogen synthase kinase 3β (Gsk-3β). Our results reveal that ER stress plays a significant role in hepatic lipid metabolism abnormalities in mice exposed to MC-LR.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China; Guangxi Zhuang Autonomous Region Forestry Science Research Institute, Nanning 530002, China.
authors.forename: Wendi
authors.initials: W
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
authors.forename: Xuxiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China. Electronic address: yangly@nju.edu.cn.
authors.forename: Liuyan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China.
authors.forename: Lizhi
authors.initials: L
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
authors.forename: Zongyao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008387:Marine Toxins; D051379:Mice; D008807:Mice, Inbred BALB C; D052998:Microcystins / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D008387:Marine Toxins; D052998:Microcystins; D011506:Proteins; D012333:RNA, Messenger; C057862:cyanoginosin LR
keywords: Endoplasmic reticulum stress; Lipid metabolism abnormality; Liver; Microcystin-LR; Toxic effect