在铁化过程中,用Hydroperoxy-PE电友分离产物形成蛋白质添加物
A A Amoscato1, T Anthonymuthu2, O Kapralov1
1Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh School of Public Health, 130 Desoto St, Pittsburgh, PA, 15261, USA.
Redox biology
|May 28, 2023
概括
铁灭症涉及氧化脂质 (PE) 与蛋白质发生反应. 识别这些PE蛋白添加物揭示了铁亡的关键参与者,这是一种细胞死亡途径,可以通过核爱素预防.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
背景情况:
- 铁亡是一种依赖于铁的细胞死亡,其特征是脂质过氧化.
- 氧化酸乙醇胺 (PE) 累积,形成独特的脂质氧化物.
- 这些氧化PE可以被截断,并与细胞蛋白反应.
研究的目的:
- 为了确定参与铁灭的氧化截断PE物种 (trPEox).
- 为了研究铁灭过程中PE蛋白添加物的形成.
- 开发一种识别PE脂氧化蛋白的方法.
主要方法:
- 雷多克斯脂质组学来识别trPEox.
- 模型测试以确定 adduct 形成.
- 基于杜拉胺素的技术,用于丰富和识别PE-脂氧化蛋白.
- 在HT-22,MLE,H9c2细胞和M2巨细胞中进行细胞研究.
- 对接模拟以评估结合亲和力.
主要成果:
- 在模型系统和ferroptotic细胞中识别了氧化截断的PE物种 (trPEox).
- 在模型中证明了trPEox和cysteine残留物之间的 adduct形成.
- 开发并使用杜拉胺技术识别数十种PE-脂氧化蛋白在不同细胞类型.
- 表明2-乙醇可以防止PE-脂氧化蛋白的形成,并阻断铁亡.
- 对接模拟表明,截断的PE有效地与已识别的蛋白质结合.
结论:
- 标识PEox-蛋白质添加物是参与ferroptosis.
- 这些添加物可以通过像2-mercaptoethanol这样的核友来预防.
- PEox蛋白添加物可能代表铁细胞细胞死亡中不可逆转的关键点.
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