Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 69, Issue 51, Pages 15716-15727Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.1c05393
Keywords
T-2 toxin; ferroptosis; SLC7A11; ROS
Funding
- National Natural Science Foundation of China [32070782, 31901667, 32072761]
- Natural Science Basic Research Program of Shaanxi [2020JQ-256]
- Chinese Universities Scientific Fund [2452021103]
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T-2 toxin induces ferroptosis by inducing lipid reactive oxygen species (ROS) and downregulating SLC7A11 expression, leading to cytotoxicity. In cells deficient in SLC7A11, T-2 toxin fails to further enhance ferroptosis, indicating the critical role of SLC7A11 in T-2 toxin-induced cytotoxicity. Ferroptosis mediates T-2 toxin-induced cytotoxicity by increasing ROS and downregulating SLC7A11 expression.
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.
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