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ToxSci Advance Access published online on November 23, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfj049
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received July 20, 2005
Accepted November 9, 2005

Environmental Toxicology

Mycotoxin Patulin Activates the p38 Kinase and JNK Signaling Pathways in Human Embryonic Kidney Cells

Biing-Hui Liu 1 *, Ting-Shuan Wu 1 {dagger}, Feng-Yih Yu 1, and Chun-Hui Wang 1

1 Department of Life Sciences, Chung Shan Medical University, Taichung, Taiwan

* To whom correspondence should be addressed.
Biing-Hui Liu, E-mail: bingliu{at}csmu.edu.tw


  Abstract

Patulin (PAT), a mycotoxin mainly produced by Penicillium and Aspergillus, is frequently detected in moldy fruits and fruit products. Exposure of human embryonic kidney (HEK293) cells to PAT led to a dose- and time-dependent increase in the phosphorylation of two major mitogen-activated protein kinases (MAPKs), p38 kinase and c-Jun N-terminal kinase (JNK). The phosphorylated forms of MAPK kinase 4 (MKK4), c-Jun, and ATF-2 were also seen in PAT-treated cultures. The cell death caused by PAT was significantly reduced by the p38 kinase inhibitor, SB203580, but not by the JNK inhibitor, SP600125. Neither p38 kinase nor JNK played a role in the PAT-induced DNA damage. In PAT-treated cells, inactivation of double-stranded RNA-activated protein kinase R (PKR) by the inhibitor, adenine, markedly suppressed JNK and ERK phosphorylation. Treatment of HEK293 cells with PAT-cysteine adduct, a chemical derivative of PAT, showed no effect on MAPK signaling pathways, cell viability, or DNA integrity. These results indicate that PAT causes rapid activation of p38 kinase and JNK in HEK293 cells, but only the p38 kinase signaling pathway contributes to the PAT-induced cell death. PKR also plays a role in PAT-mediated MAPK activation.

Keywords: patulin; p38 kinase/JNK; cell death; PKR; human embryonic kidney cells.

{dagger}equal contribution to the first author


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B.-H. Liu, T.-S. Wu, F.-Y. Yu, and C.-C. Su
Induction of Oxidative Stress Response by the Mycotoxin Patulin in Mammalian Cells
Toxicol. Sci., February 1, 2007; 95(2): 340 - 347.
[Abstract] [Full Text] [PDF]


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