在40°C的温和热应激过程中,Nrf2调解线粒体和NADPH氧化酶衍生的ROS
Georges Hraoui1, Mélanie Grondin1, Sophie Breton2
1Département des sciences biologiques, Université du Québec à Montréal, C.P. 8888, succ. Centre-ville, Montréal, Québec H3C 3P8, Canada.
Biochimica et biophysica acta. Molecular cell research
|January 12, 2025
概括
温和的热冲击触发了线粒体和NADPH氧化酶 (NOX) 的反应性氧物种 (ROS) 生产. 这种来自热量的ROS通过Nrf2激活细胞防御,Nrf2是一个关键的调节器,有助于耐热性.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 在瘤学瘤学.
背景情况:
- 过热可以提高化疗和放射治疗的疗效.
- 获得的热耐受性限制了高温症的治疗益处.
- 热耐受性激活背后的机制尚未完全理解.
研究的目的:
- 调查反应性氧物种 (ROS) 在热冲击引起的热耐受性中的作用.
- 为了确定在轻度热暴露期间ROS的来源.
- 阐明Nrf2及其调节通路在适应性细胞防御中的参与.
主要方法:
- 对HeLa细胞进行轻度热冲击 (40°C3小时).
- 线粒体抗氧化剂MitoQ和NADPH氧化酶 (NOX) 抑制剂Apocynin被用于评估ROS来源.
- 为了评估其作用,Nrf2被操纵 (过度表达/减弱)
- 测量了ROS和关键防御蛋白质 (DJ-1,PGAM5) 的水平.
主要成果:
- 轻微的热冲击增加了超氧化物和过氧化物水平,表明ROS产生.
- 线粒体和NOX都被确定为热源ROS的重要来源.
- Nrf2激活与ROS清理相关,而Nrf2倒置加剧了ROS水平.
- DJ-1和PGAM5激活似乎依赖于一个涉及Nrf2和线粒体ROS的双重系统.
结论:
- 在热应激期间,线粒体和NOX衍生的ROS对于激活Nrf2-介导的细胞防御是至关重要的.
- 这些发现突出了调节热耐受性获得的潜在治疗点.
- 了解ROS介导的适应性反应是克服癌症治疗中高温耐药性的关键.
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