| Abstract [eng] |
Irma Stašiauskaitė Study of mechanisms underlying cytochalasin E and deoxynivalenol effects in MH-22A and Jurkat cell lines SUMMARY In recent years, a great deal of interest has been generated regarding the study food safety. The Food and Agriculture Organization estimates that at least 5-10% of the world food supply is lost annually to fungi and mycotoxins – poisonous chemicals produced by microfungi during their growth on food, feeds and various agricultural commodities. The effects of mycotoxins on humans and animals are dose-related and include acute and chronic effects, in the case of some mycotoxins, carcinogenicity, mutagenicity and supression of the immune system. Deoxynivalenol, one of mycotoxines, is produced by several Fusarium genus. It can be found as natural contaminant in variuos cereal crops and in processed grains. Besides its acute and chronic toxicity and effects on immune function, deoxynivalenol contribute to gastrointestinal diseases in exposed humans. Cytochalasin E – a toxin synthesized by Aspergillus clavatus, that inhibit cell division and protein synthesis, is nephrotoxic and considered carcinogenic. The aim of this study was to assess the effects of deoxynivalenol and cytochalasin E on cell viability and to relate apoptosis to activation of signaling molecules of stress activated MAPK pathway. In our study we determined, that cytochalasin E and deoxynivalenol mechanism of action depends on cell type, concentration and time of exposure. Deoxynivalenol was marked the most potent cytotoxicity in both cell lines at greatest concentration. Meanwhile cytochalasin E showed weaker influence on cell proliferation. The activation and role of c-Jun N-terminal kinase (JNK) and p38 kinase, members of the mitogen-activated protein kineses (MAPK) family, was studied, also. Our results suggest a possible involvement of JNK in cytochalasin E induced apoptosis in Jurkat and MH-22A cells, but in deoxynivalenol treated cells this effect was inappreciable. The study of p38 MAPK activation in Jurkat and MH-22A cells after deoxynivalenol treatment revealed a markedly induced phosphorylation of this kinase that correlated with and preceded apoptosis. Our results showed that cytochalasin E didn’t provoke the activation of p38 in Jurkat cells and weak increase of phospho-p38 level in MH-22A cell line. Study of the role of protooncogene c-jun was carried out by using genetically modified MH-22A cells. The results indicated proapoptotic effect of c-jun after studied mycotoxins treatment in this cell line. |
