Induction of apoptosis and activation of JNK and p38 MAPK pathways in deoxynivalenol-treated cell lines.
Deoxynivalenol (DON) is a mycotoxin produced by what are thought to be the most prevalent toxin-producing fungi of the Fusarium genus. Here, we present the results of apoptosis induction, phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs), and expression of the c-Jun protein after DON treatment, in a pre-B lymphocyte REH cell line. In addition, human pre-T lymphocyte Jurkat, hamster kidney-derived BHK21 and mouse hepatoma MH-22a cells were used in comparative experiments in vitro. We found that the DON effect was cell origin-dependent and dose-dependent, with a significant slow-down of cell proliferation and increase of apoptotic cells in blood cell lines. BHK21 and MH-22a cells were less sensitive to the DON effect. In blood-derived REH and Jurkat cells, DON-induced apoptotic changes were preceded by an increase in JNK and p38 MAPKs phosphorylation, as well as in c-Jun expression. However, the activation of JNK phosphorylation and c-Jun expression were transient, but did not coincide with each other. An inhibitor of JNK1/2, SP600125, had a negligible negative effect on REH cell viability after DON treatment, demonstrating that JNK does not contribute to DON-induced apoptosis. In contrast, studies on the role of p38 MAPK revealed that p38 signalling is required for DON-induced apoptosis in REH cells.
Baltriukiene
Daiva
D
Institute of Biochemistry, Vilnius, Lithuania. daiva.baltriukiene@bchi.lt
Kalvelyte
Audrone
A
Bukelskiene
Virginija
V
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis*; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction; D014255:Trichothecenes / Q000633:toxicity*; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis*
D014255:Trichothecenes; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C007262:deoxynivalenol