2,2,6,6-Tetramethylpiperidine-1-oxyl acts as a volatile inhibitor of ferroptosis and neurological injury
2,2,6,6-Tetramethylpiperidine-1-oxyl acts as a volatile inhibitor of ferroptosis and neurological injury
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2,2,6,6-四甲基哌啶-1-氧基作为铁死亡和神经损伤的挥发性抑制剂
DOI：
10.1093/jb/mvac044
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Torii Seiji
中科院分区：
文献类型：
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作者：
Mizuno Hiroyuki;Kubota Chisato;Takigawa Yuta;Shintoku Ryosuke;Kannari Naokatsu;Muraoka Takako;Obinata Hideru;Yoshimoto Yuhei;Kanazawa Masato;Koshiishi Ichiro;Torii Seiji
铁凋亡是一种氧化应激细胞死亡，与几种疾病的细胞损伤有关，用特异性抑制剂治疗已被证明可以保护细胞和组织。在这里，我们证明了与氮氧自由基，2，2，6，6-四甲基哌啶-N-氧基（克里思）的治疗，防止在空气中的方式的铁凋亡细胞死亡。其他克里思衍生物和亲脂性抗氧化剂，如Trolox和ferrostatin-1，也阻止了由erastin和RSL 3诱导的细胞死亡;然而，只有克里思从物理上遥远的位置表现出抑制活性。克里思蒸发而不分解，然后再次溶解到附近的水溶液中。挥发的克里思抑制小鼠海马细胞系中谷氨酸诱导的细胞死亡，并且还减少小鼠缺血模型中的神经元细胞死亡。这些结果表明，克里思是一种独特的细胞保护剂，以挥发性介导的方式发挥作用。
Ferroptosis, a type of oxidative stress cell death, has been implicated in cell injury in several diseases, and treatments with specific inhibitors have been shown to protect cells and tissues. Here we demonstrated that a treatment with the nitroxide radical, 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), prevented the ferroptotic cell death in an airborne manner. Other TEMPO derivatives and lipophilic antioxidants, such as Trolox and ferrostatin-1, also prevented cell death induced by erastin and RSL3; however, only TEMPO exhibited inhibitory activity from a physically distant location. TEMPO vaporized without decomposing and then dissolved again into a nearby water solution. Volatilized TEMPO inhibited glutamate-induced cell death in mouse hippocampal cell lines and also reduced neuronal cell death in a mouse ischemia model. These results suggest that TEMPO is a unique cell protective agent that acts in a volatility-mediated manner.