Nasri Thanakarn, Bosch Remko R, Voorde Sandra ten, Fink-Gremmels Johanna
Department of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Utrecht University, NL 3508 TD Utrecht, The Netherlands.
Toxicol In Vitro. 2006 Sep;20(6):832-40. doi: 10.1016/j.tiv.2006.01.003. Epub 2006 Feb 10.
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.
多项研究表明，霉菌毒素T-2毒素、二醋酸雪腐镰刀菌烯醇（DAS）、脱氧雪腐镰刀菌烯醇（DON）和雪腐镰刀菌烯醇（NIV）会影响淋巴细胞功能。然而，这些单端孢霉烯族毒素免疫调节作用的分子机制尚未明确。在本研究中，检测了A型单端孢霉烯族毒素T-2毒素和DAS，以及B型单端孢霉烯族毒素DON（及其代谢产物脱环氧脱氧雪腐镰刀菌烯醇；DOM-1）和NIV降低线粒体活性以及诱导Jurkat T细胞（人T淋巴细胞）凋亡的能力。如AlamarBlue细胞毒性试验所示，T-2毒素和DAS在低浓度时的细胞毒性比DON和NIV大得多。此外，我们观察到磷脂酰丝氨酸外化、细胞色素c从线粒体释放、procaspase-3降解和Bcl-2降解，表明DON和NIV诱导细胞毒性的机制主要是通过凋亡。相比之下，A型单端孢霉烯族毒素降低线粒体活性的浓度比B型单端孢霉烯族毒素低约1000倍，从而导致坏死。这些数据表明，A型和B型单端孢霉烯族毒素产生细胞毒性作用的机制不同。
