多氧化剂环境作为髓氧化酶的自杀性抑制剂
Ramona Clemen1, Lara Minkus1, Debora Singer1,2
1ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany.
Antioxidants (Basel, Switzerland)
|November 25, 2023
概括
炎症涉及到修改蛋白质的反应性物种. 这项研究表明,将髓氧化酶 (MPO) 暴露在血生成的活性物种中,通过引起氧化后翻译性修饰,使其酶活性失活.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 血医学是一种血医学.
背景情况:
- 组织炎症涉及天生的免疫细胞产生反应性物种.
- 中性粒细胞释放髓氧化酶 (MPO),产生低酸 (HOCl) 和其他氧化剂.
- 多种反应性物种对MPO功能的影响尚不清楚.
研究的目的:
- 调查多氧化剂环境对人类MPO的影响.
- 分析MPO的氧化后翻译修饰 (oxPTMs) 和结构变化.
- 为了确定这些修改对MPO酶活性的影响.
主要方法:
- 人类的MPO暴露在体温下由等离子体产生的活性物种中.
- 使用各种气体混合物来创建不同的反应性物种配置文件.
- 使用动态光散射,CD光谱学和质谱学分析MPO,以评估oxPTMs,结构和活性.
主要成果:
- 在所有测试的血条件下,MPO活性显著降低.
- 蛋白质结构分析表明MPO的寡合化.
- 质谱测量确定了各种oxPTMs,包括甲氨酸和氨酸氧化和氨酸脱化,与MPO无活化相关.
结论:
- 由等离子体生成的活性物种在MPO上诱导显著的oxPTM.
- 这些修改,特别是囊氧化和氨酸脱化,导致形状变化和MPO无活化.
- 这突显了血在炎症条件下调节MPO活性的潜力.
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