Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA, 92037, USA.
Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA, 92037, USA.
Free Radic Biol Med. 2021 Aug 1;171:219-231. doi: 10.1016/j.freeradbiomed.2021.05.023. Epub 2021 May 16.
Ferroptosis was first described in 2012 as an iron- and lipid peroxidation-dependent form of regulated cell death. Since its initial description, these two characteristics have informed numerous cell culture studies where inhibitors of lipid peroxidation and/or iron chelators have been shown to prevent cell death induced by a wide range of insults. However, it is not clear whether these two characteristics are sufficient to distinguish ferroptosis from other forms of regulated cell death. Thus, the primary goal of this study was to determine whether a unique combination of features could be identified that would provide an approach to more clearly separate ferroptosis from other forms of regulated cell death. To this end, multiple pharmacological inhibitors based on a variety of studies were tested. Many of these inhibitors were previously shown to protect cells from oxytosis, a regulated cell death pathway that mechanistically overlaps with ferroptosis and is induced by some of the same chemicals as ferroptosis. These inhibitors were not only tested against both known ferroptosis and oxytosis inducers but also a number of other insults that have been suggested to induce ferroptosis. The results show that a pharmacological fingerprint for ferroptosis can be established and used to categorize toxic insults into those that overlap with oxytosis/ferroptosis and those that do not.
铁死亡于 2012 年首次被描述为一种依赖铁和脂质过氧化的调节性细胞死亡形式。自最初描述以来，这两个特征已经为大量细胞培养研究提供了信息，其中已经表明，脂质过氧化抑制剂和/或铁螯合剂可以预防广泛的刺激物诱导的细胞死亡。然而，目前尚不清楚这两个特征是否足以将铁死亡与其他形式的调节性细胞死亡区分开来。因此，本研究的主要目标是确定是否可以识别出独特的组合特征，从而提供一种更清晰地区分铁死亡与其他形式的调节性细胞死亡的方法。为此，测试了基于各种研究的多种药理学抑制剂。其中许多抑制剂先前已被证明可保护细胞免受氧化细胞死亡，这是一种与铁死亡在机制上重叠的调节性细胞死亡途径，并且由与铁死亡相同的一些化学物质诱导。这些抑制剂不仅针对已知的铁死亡和氧化细胞死亡诱导剂进行了测试，还针对其他一些被认为可诱导铁死亡的刺激物进行了测试。结果表明，可以建立铁死亡的药理学特征，并将有毒刺激物分类为与氧化细胞死亡/铁死亡重叠的刺激物和不重叠的刺激物。
