Impact of DUSP1 on the apoptotic potential of deoxynivalenol in the epithelial cell line HepG2.
The trichothecene deoxynivalenol (DON) is the most common mycotoxin contaminant of cereal-based food products. Several studies revealed DON as a potent inducer of the three major mitogen-activated protein kinases (MAPKs). Until now, little is known about the role of negative regulators of MAPK pathway in the cellular response to DON. In this report we evaluated, for the first time, the impact of mitogen-activated protein kinase phosphatases (MKPs), particularly dual specific phosphatase 1 (DUSP1), on the toxic potential of DON in the epithelial cell line HepG2. Our results indicate that both low and high concentrations of DON trigger a strong and sustained DUSP1 mRNA and protein expression, mediated by the sustained activation of MEK/ERK pathway. Furthermore, the expression of DUSP1 protein correlates with the inactivation of JNK1/2, whereas a sustained activation of p38 and ERK1/2 was observed in the presence of DON. In contrast, treatment of DUSP1 knock-down cells with DON triggers a prolonged activation of JNK1/2, which leads to the induction of apoptosis. Taken together, we propose DUSP1 as a novel target gene of DON, which is essential for the prevention of DON induced apoptosis in the epithelial cell line HepG2.
Casteel
Maximilian
M
Department of Veterinary Sciences, Ludwig-Maximilians-University of Munich, Schönleutnerstrasse 8, 85764 Oberschleissheim, Germany. m.casteel@mh.vetmed.uni-muenchen.de
Nielsen
Carina
C
Kothlow
Sonja
S
Dietrich
Richard
R
Märtlbauer
Erwin
E
D017209:Apoptosis / Q000187:drug effects*; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014255:Trichothecenes / Q000633:toxicity*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D012333:RNA, Messenger; D014255:Trichothecenes; D048031:JNK Mitogen-Activated Protein Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; C007262:deoxynivalenol