Mechanism Of Apoptosis Induced By Deoxynivalenol

Deoxynivalenol (DON) is one of several mycotoxins produced by certainFusarium species that frequently infect corn, wheat, oats, barley, rice, and other grainsin the field or during storage. The exposure risk to human is directly through foods ofplant origin (cereal grains) or indirectly through foods of animal origin (kidney, liver,milk, eggs). All animal species evaluated to date are susceptible to DON according tothe rank order of pigs>mice> rats> poultry﹥ruminants. DON affects animal andhuman health causing acute temporary nausea, vomiting, diarrhea, abdominal pain,headache, dizziness, and fever. In addition to its acute effects, chronic dietaryexposure to DON causes impaired weight gain, anorexia, decreased nutritionalefficiency and immune dysregulation in experimental animals. DON can preventpolypeptide chain initiation or elongation by interaction with eukaryotic60sribosomes and inhibit protein synthesis. DON are extremely toxic to leukocytes andother rapidly dividing cells and can induce apoptosis at the cellular level.cytotoxicand apoptotic capacities of DON can be related to the activation of three groups ofMAPKs (SAPK/JNKs, p38MAPK, ERK1/2). Trichothecenes are both immuno-stimulatory or immunosuppressive depending on dose, frequency and duration ofexposure as well as type of immune function assay. These observations are importantbecause they provide insight into possible mechanisms by which the DON couldcontribute to manifestations associated with diseases.This study included two parts: one was the toxity of DON to Hela and Changliver cells in vitro and another was the experiment with KM mice in vivo. The aim ofthis research was to further explore the efferts of DON on the apoptosis.Firstly, thisresearch was studied with MTT assay, FCM method, western blot, the activity ofcaspase3respectly to detect the cells morpholohical changes, apoptosis, the proteinexpression and activity changes of caspase3, after Hela and Chang liver cells weretreated with DON at different concentrations and different times. In this study, thegene jnk was cloned and the fluorescence vector pEGFP-N1-jnk was constructed to beused for the cellular localization. The aim of this experiment was to detect the activity of JNK in the DON-induced apoptosis process. In vivo, we used the extracted DONcrude toxin to treat the mice by intraperitoneal injection to detect body weightchanges, blood biochemical parameters and organ changes. This paper studied theapoptosis induced by DON and revealed the pro-apoptotic effect of DON and itsmolecular mechanism.The results:①From the results of cell morphology, MTT cell proliferationand cytoxicity testing, as well as apoptotic FCM assay, we can conclude DON canenhance apoptosis of Hela and Chang liver cells in a concentration-dependent andtime-dependent manner.②The JNK signaling pathway was activated inDON-induced apoptosis process. JNK involved in the DON-induced apoptosisprocess, but the molecular mechanism needs further study.③Caspase3activity wassignificantly increased of DON-induced apoptosis.④The concentration of extractedDON crude toxin detected by ELISA is3.273mg/mL.⑤DON consumptionreduced weight gain in mice, and some blood biochemical parameters changed.