Induction of oxidative stress response by the mycotoxin patulin in mammalian cells.
Patulin (PAT), a mycotoxin mainly produced by Penicillium and Aspergillus, is found in various foods and feeds. In the present study, its effects on oxidative stress in various mammalian cell lines were investigated. When cell-permeating fluorescent dyes were used as indicators of the generation of reactive oxygen species (ROS), we found that PAT treatment directly increased intracellular oxidative stress in human embryonic kidney (HEK293) and human promyelocytic leukemia (HL-60) cells. Lipid peroxidation levels were also significantly increased in HL-60 cells and mouse kidney homogenates treated with PAT. Suppression of CuZn-superoxide dismutase (SOD) expression in mammalian cells by small interfering RNA resulted in an increase in PAT-mediated membrane damage, while overexpression of human CuZn-SOD or catalase led to a reduction in damage, indicating the involvement of ROS in PAT toxicity. Pretreatment of HEK293 cells with Tiron, a free radical scavenger, reduced the phosphorylation levels of extracellular signal-regulated kinase (ERK) 1/2 elicited by PAT. The ERK1/2 signaling pathway inhibitor, U0126, also significantly decreased the levels of ROS associated with PAT treatment. These findings indicate that PAT treatment results in the ROS production in mammalian cells, and ROS partially contributes to PAT-induced cytotoxicity. Activation of ERK1/2 signaling pathway is correlated with PAT-mediated ROS.
Liu
Biing-Hui
BH
Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan, ROC. bingliu@csmu.edu.tw
Wu
Ting-Shuan
TS
Yu
Feng-Yih
FY
Su
Ching-Chyuan
CC
D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D002374:Catalase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010365:Patulin / Q000633:toxicity*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D010365:Patulin; D002374:Catalase; D013482:Superoxide Dismutase; D048049:Extracellular Signal-Regulated MAP Kinases