奥克拉托克素A通过破坏铁的平衡和增加ROS诱导细胞铁亡
Sen Wang1, Hui Ren1, Chen Fan1
1International Cooperation Joint Laboratory of Jiangsu Province Colleges and Universities, School of Life Sciences, Jiangsu Normal University, Xuzhou, Jiangsu Province 221116, China.
奥克拉托克素A (OTA) 通过破坏铁的平衡,导致细胞死亡,导致过度的氧化应激. 铁化有效地保护了细胞,揭示了铁.
科学领域:
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
- 食品安全 食品安全
背景情况:
- 毒素A (OTA) 是一种普遍存在的食品污染物,已知具有毒性作用.
- 导致OTA引起的损伤的确切机制,特别是氧化应激,仍然不完全理解.
- 细胞内铁失调与各种细胞死亡途径有关,包括铁亡.
研究的目的:
- 为了研究细胞内铁在甲素A诱导的活性氧物种 (ROS) 积累中的作用.
- 为了确定OTA是否会诱导人类细胞中依赖铁的ferroptotic细胞死亡.
- 为了阐明OTA对细胞铁平衡的影响.
主要方法:
- 已经使用的人类细胞系暴露于毒素A.
- 评估细胞活力,铁灭标志物和细胞内铁水平.
- 分析了铁代谢调节者的基因和蛋白质表达 (TFR1,FTH,FPN,Hepcidin).
- 在机械学研究中使用铁化剂和ROS吸尘器.
主要成果:
- 奥克拉托辛A治疗诱导了铁亡的特征和细胞活力降低.
- 通过对铁进口 (TFR1,FTH) 的上调和对铁出口 (FPN) 的下调,OTA扰乱了铁的稳态,增加了肝素.
- 在OTA暴露后观察到细胞内铁积累,ROS升高和脂质过氧化.
- 铁化显著改善了OTA诱导的毒性,铁过载和ROS产量.
- ROS清理器部分逆转了OTA的影响,表明与铁失调相比,其作用是次要的.
结论:
- 奥克拉托克素A诱导细胞中的铁细胞死亡,主要是通过破坏铁的平衡.
- 由OTA诱导的细胞内铁积累是氧化应激和随后的细胞死亡的关键驱动因素.
- 准铁代谢是一种潜在的治疗策略,可以对抗甲毒素A的神经毒性.
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