Oxidative stress and DNA interactions are not involved in Enniatin- and Beauvericin-mediated apoptosis induction
Oxidative stress and DNA interactions are not involved in Enniatin- and Beauvericin-mediated apoptosis induction
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DOI：
10.1002/mnfr.200800571
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发表时间：
2009-09-01
影响因子：
5.2
通讯作者：
Berger, Walter
中科院分区：
文献类型：
--
作者：
Dornetshuber, Rita;Heffeter, Petra;Berger, Walter
镰刀菌毒素beauvericin （BEA）和结构相关菌素（ENN）是谷物食品和饲料中常见的污染物。它们在诱导细胞凋亡的基础上发挥强大的细胞毒活性。由于已知活性氧（ROS）和DNA损伤导致凋亡细胞死亡，本研究旨在阐明是否。氧化应激和DNA相互作用参与了ENN-和bea诱导的细胞毒性。多种细胞和分子分析表明，氧化应激不会导致ENN-和bea诱导的细胞毒性。相反，这两种镰刀菌毒素显示出适度的抗氧化活性。此外，只有在高浓度（100 μ M）下，这两种真菌毒素才能大量插入dsDNA，并抑制拓扑异构酶I和II的催化活性。此外，ENN和BEA的有效细胞毒活性被证明广泛独立于细胞错配和核苷酸切除修复途径。此外，共济失调毛细血管扩张突变（ATM）蛋白激酶，一种众所周知的DNA损伤传感器，不影响BEAs的细胞毒性电位，而在enn诱导的细胞毒性中，ATM有可检测到的但不是主要的调节影响。总之，我们的数据表明，rid和DNA损伤不是ENN和bea介导的细胞毒性的关键因素。
The fusariotoxins beauvericin (BEA) and the structurally related enniatins (ENN) are frequent contaminants of grain-based food and feed. They exert potent cytotoxic activities based on apoptosis induction. Since it is known, that reactive oxygen species (ROS) and DNA damage lead to apoptotic cell death, this study aimed to clarify whether. oxidative stress and DNA interactions are involved in ENN- and BEA-induced cytotoxicity. Diverse cellular and molecular assays indicated that oxidative stress does not contribute to ENN- and BEA-induced cytotoxicity. In contrast, both fusariotoxins were shown to exert moderate antioxidative activities. Moreover, only at high concentrations (>100 mu M) both mycotoxins were found to intercalate substantially into dsDNA and to inhibit the catalytic activity of topoisomerase I and II. Furthermore, the potent cytotoxic activity of ENN and BEA was shown to be widely independent of cellular mismatch- and nucleotide excision repair pathways. Also the ataxia-telangiectasia mutated (ATM) protein kinase, a well known DNA damage sensor, did not affect BEAs cytotoxic potential while in ENN-induced cytotoxicity ATM had a detectable but not a major modulating influence. Together, our data suggest that RIDS and DNA damage are not key factors in ENN- and BEA-mediated cytotoxicity.