Microcystin-LR altered mRNA and protein expression of endoplasmic reticulum stress signaling molecules related to hepatic lipid metabolism abnormalities in mice

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 mu g/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 mu g/kg/d MC-LR altered serum lipid parameters and caused hepatic steatosis. MC-LR treatment at 10 or 20 mu g/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 2 alpha (eIF-2 alpha) kinase (PERK), and eIF-2 alpha. MC-LR exposure at 10 or 20 mu g/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 acetylcoenzyme A carboxylase a (ACACA) and glycogen synthase kinase 313 (Gsk-30). Our results reveal that ER stress plays a significant role in hepatic lipid metabolism abnormalities in mice exposed to MC-LR. (C) 2015 Elsevier B.V. All rights reserved.