Fumonisin B 1 -induced oxidative stress triggers Nrf2-mediated antioxidant response in human hepatocellular carcinoma (HepG2) cells

AbstractFumonisin B1 (FB1), a causative agent for animal-related mycotoxicoses, has been implicated in human and animal cancer. FB1 induces oxidative stress but the related survival responses are not well established. Central to this response is the transcription factor, nuclear factor erythroid 2 p45 –related factor 2 (Nrf2). The effects of FB1 on Nrf2-related survival responses in human hepatoma (HepG2) cells were investigated. HepG2 cells were treated with 200  μmol/l FB1 (IC50–24 h). Cellular redox status was assessed via the quantification of intracellular reactive oxygen species (ROS), lipid peroxidation, protein oxidation and the antioxidant glutathione (GSH). The protein expression of oxidative stress and mitochondrial stress response proteins [Nrf2, phosphorylate d-Nrf2 (pNrf2), superoxide dismutase 2 (SOD2), catalase (CAT), sirtuin 3 (Sirt 3) and Lon-protease 1 (Lon-P1)] were quantified by western blotting, while gene expression levels ofSOD2,CAT andGPx were assessed using quantitative polymerase chain reaction (qPCR). Lastly, the fluorometric, JC-1 assay was used to determine mitochondrial polarisation. FB1 significantly increased ROS (p ≤ 0.001), and induced lipid peroxidation (p <  0.05) and protein carbonylation (p ≤ 0.001), which corresponded with the increase in GSH levels (p <  0.05). A significant increase in pNrf2, SOD2,SOD2, CAT (p <  0.05),CAT (p ≤ 0.01) andGPx (p ≤ 0.001) expression was observed; howeve...
Source: Mycotoxin Research - Category: Toxicology Source Type: research