Differential induction of apoptosis by type A and B trichothecenes in Jurkat T-lymphocytes.
Several studies have shown that the mycotoxins T-2 toxin, diacetoxyscirpenol (DAS), deoxynivalenol (DON) and nivalenol (NIV) affect lymphocyte functioning. However, the molecular mechanisms underlying the immunomodulatory effects of these trichothecenes are not defined yet. In this study, the potency of the type A trichothecenes T-2 toxin and DAS, and the type B trichothecenes DON (and its metabolite de-epoxy-deoxynivalenol; DOM-1) and NIV to reduce mitochondrial activity and to induce apoptosis of Jurkat T cells (human T lymphocytes) were examined. T-2 toxin and DAS are much more cytotoxic at low concentrations than DON and NIV as shown by the AlamarBlue cytotoxicity assay. In addition, the mechanism whereby DON and NIV induced cytotoxicity is mainly via apoptosis as we observed phosphatidylserine externalization, mitochondrial release of cytochrome c, procaspase-3 degradation and Bcl-2 degradation. In contrast, type A trichothecenes reduce the mitochondrial activity at approximately 1000-fold lower concentrations than the type B trichothecenes, resulting in necrosis. These data suggest that the mechanisms resulting in cytotoxic effects are different for type A and type B trichothecenes.
Nasri
Thanakarn
T
Department of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Utrecht University, NL 3508 TD Utrecht, The Netherlands.
Bosch
Remko R
RR
Voorde
Sandra ten
St
Fink-Gremmels
Johanna
J
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D014255:Trichothecenes / Q000633:toxicity*
D014255:Trichothecenes; C038405:nivalenol; C007262:deoxynivalenol; C001809:diacetoxyscirpenol