氧化性修饰控制异常的氨酸激酶活性.
Paul Schulan1, Kristian Wende1, Thomas von Woedtke1,2
1ZIK plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Strasse 2, Greifswald 17489, Germany.
Biointerphases
|December 2, 2024
概括
癌症治疗耐药性可能与瘤微环境 (TME) 中过多的活性氧物种 (ROS) 有关. 这项研究使用气体等离子体来证明ROS可以通过引起氧化修饰来降低氨酸激酶 (TK) 活性.
科学领域:
- 生物化学和分子生物学
- 癌症研究 癌症研究
- 生物医学工程 生物医学工程
背景情况:
- 癌症中耐疗性是一个重大的临床挑战,通常与瘤微环境 (TME) 相关.
- TME经常表现出高水平的活性氧物种 (ROS),这些物种可以修改癌症治疗中至关重要的蛋白质,如氨酸激酶 (TKs).
- 由于复制复杂的ROS条件的困难,了解TME中ROS诱导的蛋白质修饰是有限的.
研究的目的:
- 使用气体等离子技术模拟亲氧化TME条件.
- 研究ROS对关键治疗点的功能影响,特别是三种氨酸激酶 (TKs).
- 识别和量化由ROS.引起的TK的氧化后翻译性修饰 (oxPTMs).
主要方法:
- 气体等离子体被用来产生多种ROS类型的高度,模拟TME条件.
- 三个临床相关的试验基因 (EGFR,SRC,VEGFR2) 被暴露在液体溶液中的气体血中.
- 使用高分辨率质谱分析等离子体处理的TKs对oxPTMs进行分析,并使用内部数据库进行识别.
主要成果:
- 对气体等离子体的暴露导致了TK活动的显著减少.
- 质谱学在TC上发现了许多oxPTM,特别是在含硫和芳香氨基酸残留物上.
- 氧化发生在功能重要部位,包括ATP结合口袋和TK抑制剂向的区域.
结论:
- 气体等离子体有效地模仿TME亲氧化条件,并在TKs上诱导显著的oxPTM.
- 通过改变关键的结构和催化残留物,ROS诱导的修饰可以损害TK功能.
- 这些发现表明,TME中ROS水平升高可能导致TCK活性降低和治疗抵抗.
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