In vitro and in vivo effects of deoxynivalenol (DNV) on regulators of cap dependent translation control in porcine endometrium.
Deoxynivalenol (DNV) is the most frequently encountered trichothecene in grain-based foods, and is able to produce toxic effects resulting in various diseases in farm and laboratory animals. The molecular mechanisms that control this mycotoxin mediated effects in porcine endometrial cells are far from being completely understood. Recent results show that DNV inhibits protein synthesis in actively proliferating tissues. Therefore, the present study investigated the effects of this mycotoxin on a cellular level in an in vivo and in vitro system. The abundance and phosphorylation state (activity) of the cell cycle dependent kinases MAPk and Akt (PKB) and their potential targets eIF-4E (eukaryotic initiation factor 4E) and 4E-BP1 (4E binding protein, eIF4E repressor protein) were examined. In previous investigations it was found that these factors are involved in initiation of mRNA translation. The results show that DNV in vitro strongly reduce the abundance of p38 MAPk, protein kinase Akt and the alpha- and beta-4E-BP1 bands. The phosphorylation state of these proteins was obviously not modulated. In contrast, the eIF4E phosphorylation was strongly reduced in DNV treated cells. In summary, our in vitro results let assume that DNV potentially influences gene expression, but this work does not present a direct proof that DNV alters processes, which are involved in the initiation of mRNA translation. Surprisingly in vivo, an influence of DNV feeding on the investigated molecular events could not be demonstrated.
Wollenhaupt
K
K
Unit of Reproductive Biology, Research Institute for the Biology of Farm Animals, 18196 Dummerstorf, Germany. wollenhaupt@fbn-dummerstorf.de
Dänicke
S
S
Brüssow
K-P
KP
Tiemann
U
U
D000818:Animals; D002478:Cells, Cultured; D004032:Diet; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D005260:Female; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013552:Swine; D014255:Trichothecenes / Q000633:toxicity*; D014908:Triticum; D014404:Tubulin / Q000378:metabolism
D039561:Eukaryotic Initiation Factor-4E; D010750:Phosphoproteins; D014255:Trichothecenes; D014404:Tubulin; D017346:Protein Serine-Threonine Kinases; C007262:deoxynivalenol