Defining a pharmacological inhibitor fingerprint for oxytosis/ferroptosis.
Defining a pharmacological inhibitor fingerprint for oxytosis/ferroptosis.
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DOI：
10.1016/j.freeradbiomed.2021.05.023
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发表时间：
2021-08-01
影响因子：
7.4
通讯作者：
Maher P
中科院分区：
文献类型：
--
作者：
Soriano-Castell D;Currais A;Maher P
2012年，铁凋亡被首次描述为一种铁和脂质过氧化依赖性的调节性细胞死亡形式。自其最初描述以来，这两个特征已经告知了许多细胞培养研究，其中脂质过氧化和/或铁螯合剂的抑制剂已被证明可以防止由广泛的损伤诱导的细胞死亡。然而，目前尚不清楚这两个特征是否足以将铁凋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鉴定出一种独特的特征组合，该组合将提供一种方法，以更清楚地将铁凋亡与其他形式的受调节的细胞死亡分开。为此，基于各种研究测试了多种药理学抑制剂。这些抑制剂中的许多以前被证明可以保护细胞免受氧化作用，这是一种受调节的细胞死亡途径，在机械上与铁凋亡重叠，并且由与铁凋亡相同的化学物质诱导。这些抑制剂不仅针对已知的铁凋亡和氧化诱导剂进行了测试，而且还针对已被建议诱导铁凋亡的许多其他损伤进行了测试。结果表明，可以建立铁蛋白缺乏症的药理学指纹，并用于将毒性损伤分类为与氧化/铁蛋白缺乏症重叠的损伤和不重叠的损伤。
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.
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ACSL4 通过塑造细胞脂质成分来决定铁死亡敏感性。
影响因子：
14.8
作者：
Doll S;Proneth B;Tyurina YY;Panzilius E;Kobayashi S;Ingold I;Irmler M;Beckers J;Aichler M;Walch A;Prokisch H;Trümbach D;Mao G;Qu F;Bayir H;Füllekrug J;Scheel CH;Wurst W;Schick JA;Kagan VE;Angeli JP;Conrad M
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Conrad M
影响因子：
64.5
作者：
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通讯作者：
Stockwell BR
影响因子：
16.6
作者：
Kang, Yunyi;Tiziani, Stefano;Park, Goonho;Kaul, Marcus;Paternostro, Giovanni
通讯作者：
Paternostro, Giovanni
影响因子：
7.3
作者：
Chiruta, Chandramouli;Schubert, David;Dargusch, Richard;Maher, Pamela
通讯作者：
Maher, Pamela
影响因子：
5.3
作者：
Ishige, K;Chen, Q;Schubert, D
通讯作者：
Schubert, D