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ToxSci Advance Access originally published online on November 7, 2006
Toxicological Sciences 2007 95(2):340-347; doi:10.1093/toxsci/kfl156
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Induction of Oxidative Stress Response by the Mycotoxin Patulin in Mammalian Cells

Biing-Hui Liu*,1, Ting-Shuan Wu*, Feng-Yih Yu* and Ching-Chyuan Su{dagger}

* Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan, ROC {dagger} Tian-Sheng Memorial Hospital, Tong Kong, Ping-Tong, Taiwan, ROC

1 To whom correspondence should be addressed at Department of Biomedical Sciences, Chung Shan Medical University, No. 110, Sec. 1, Chien-Kuo N. Road, Taichung, 402 Taiwan, ROC. Fax: +886 4-24757412. E-mail: bingliu{at}csmu.edu.tw.

Received August 5, 2006; accepted October 17, 2006


  Abstract

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.

Key Words: patulin; reactive oxygen species; siRNA; CuZn-SOD; catalase; ERK1/2 signaling; mycotoxin.


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