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如何使ROS诱导NETosis? 氧化性DNA损伤,DNA修复和染色体脱凝

Dhia Azzouz¹, Nades Palaniyar^1,2,3

¹Translational Medicine, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

|October 26, 2024

概括

中性细胞外细胞陷 (NETs) 是类似网状的DNA结构,对防御至关重要,但与疾病有关. 它们的形成 (NETosis) 涉及活性氧物种 (ROS) 和DNA修复,复杂的相互作用影响各种条件.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
生物化学生物化学

背景情况:

中性粒细胞外细胞陷 (NETs) 是基于DNA的结构,由中性粒细胞在NETosis期间释放出来,这是一个受调节的细胞死亡过程.
网对于抗微生物防御至关重要,但也会导致自身免疫性疾病和组织损伤.
网症严重依赖于反应性氧物种 (ROS) 生产,源自NADPH氧化酶 (NOX) 或线粒体路径.

研究的目的:

阐明反应性氧物种 (ROS) 生产,DNA修复机制和中性粒细胞外细胞陷 (NET) 形成之间的复杂相互作用.
研究不同刺激和条件如何调节NETosis中ROS生成和DNA修复之间的平衡.
通过了解在各种病理背景下NET形成的调节机制,识别潜在的治疗点.

主要方法:

在NETosis中研究了ROS生产途径 (NOX依赖和NOX独立).
研究了DNA修复过程在不同NETosis模型中的作用,包括UV诱导的apoNETosis,离子体刺激,细菌感染和自发NETosis.
在不同阶段利用DNA修复抑制剂来评估它们对NET形成的影响.

主要成果:

紫外线辐射通过线粒体ROS和DNA修复触发aponetosis.
ROS和DNA修复都是离子体诱导的NETosis的关键,尽管它们的作用是局部的.
早期的DNA修复对细菌感染诱导的NETosis至关重要,而在无血清条件下的自发NETosis是由早期的DNA修复抑制而停止,但通过后期的抑制而增强.
在DNA修复和ROS产生的微妙平衡中,调节了NET的形成,并激活了依赖刺激的通路.

结论:

网的形成是由ROS生产和DNA修复途径之间的相互作用复杂地调节的.
不同的刺激激活ROS源和DNA修复过程的不同组合,以控制NETosis.
了解这些调节机制为涉及NET的疾病提供了潜在的治疗策略.

关键词:

造成的DNA损伤是DNA损伤.修复DNA的修复DNA的修复形成了NET,形成了NET.在NET形成 (ApoNETosis) 过程中发生亡.天生的免疫蛋白质是天生的免疫蛋白质.线粒体中的线粒体.分子机制的分子机制.反应性氧物种 (ROS) 是一种反应性氧物种.转录的发射发生在转录中.

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