T-2 毒素通过增加脂质活性氧种类 (ROS) 和下调溶质载体家族 7 成员 11 (SLC7A11) 来诱导铁死亡,Journal of Agricultural and Food Chemistry

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T-2 毒素通过增加脂质活性氧种类 (ROS) 和下调溶质载体家族 7 成员 11 (SLC7A11) 来诱导铁死亡
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2021-12-17 , DOI: 10.1021/acs.jafc.1c05393
Guoyan Wang ₁ , Senlin Qin ₁ , Yining Zheng ₁ , Chao Xia ₁ , Pei Zhang ₁ , Linxuan Zhang ₂ , Junhu Yao ₁ , Yanglei Yi ₂ , Lu Deng ₁

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T-2 毒素是一种常见于动物饲料和农产品中的单端孢霉烯真菌毒素。有证据表明 T-2 毒素诱导细胞凋亡和自噬。这项研究调查了铁死亡在 T-2 毒素细胞毒性中的作用。RAS 选择性致死化合物 3 (RSL3) 和 Erastin 用于启动铁死亡。T-2 毒素增强了 RSL3 和 Erastin 引发的细胞死亡。用铁死亡抑制剂 ferrostatin-1 治疗显着恢复了 T-2 毒素对 RSL3 或 Erastin 启动的细胞凋亡的敏化作用，表明铁死亡在 T-2 毒素诱导的细胞毒性中起着至关重要的作用。从机制上讲，T-2 毒素通过诱导脂质活性氧 (ROS) 促进铁死亡，如N-乙酰-l-半胱氨酸显着阻断了 T-2 毒素诱导的铁死亡。此外，T-2 毒素降低了溶质载体家族 7 成员 11 (SLC7A11) 的表达，并且未能进一步增强 SLC7A11 缺陷细胞中的铁死亡。SLC7A11 过表达显着挽救了由 T-2 毒素引起的增强的铁死亡。T-2 毒素通过下调 SLC7A11 表达诱导铁死亡。铁死亡通过增加 ROS 和下调 SLC7A11 表达来介导 T-2 毒素诱导的细胞毒性。

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T-2 Toxin Induces Ferroptosis by Increasing Lipid Reactive Oxygen Species (ROS) and Downregulating Solute Carrier Family 7 Member 11 (SLC7A11)

T-2 toxin is a trichothecene mycotoxin commonly found in animal feed and agricultural products. Evidence indicates that T-2 toxin induces apoptosis and autophagy. This study investigated the role of ferroptosis in T-2 toxin cytotoxicity. RAS-selective lethal compound 3 (RSL3) and Erastin were applied to initiate ferroptosis. RSL3- and Erastin-initiated cell death were enhanced by T-2 toxin. Treatment with the ferroptosis inhibitor ferrostatin-1 markedly restored the sensitizing effect of T-2 toxin to RSL3- or Erastin-initiated apoptosis, suggesting that ferroptosis plays a vital role in T-2 toxin-induced cytotoxicity. Mechanistically, T-2 toxin promoted ferroptosis by inducing lipid reactive oxygen species (ROS), as N-acetyl-l-cysteine significantly blocked T-2 toxin-induced ferroptosis. Moreover, T-2 toxin decreased the expression of solute carrier family 7 member 11 (SLC7A11) and failed to further enhance ferroptosis in SLC7A11-deficient cells. SLC7A11 overexpression significantly rescued the enhanced ferroptosis caused by T-2 toxin. T-2 toxin induces ferroptosis by downregulating SLC7A11 expression. Ferroptosis mediates T-2 toxin-induced cytotoxicity by increasing ROS and downregulating SLC7A11 expression.

更新日期：2021-12-29

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