通过半机械计算建模解读NRF2和SRXN1之间的定量关系
Raju Prasad Sharma1, Liesanne Loonstra-Wolters1, Bas Ter Braak1
1Division of Cell Systems and Drug Safety, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, Leiden 2333 CC, the Netherlands.
Toxicology
|September 19, 2025
概括
核因子红色素2相关因子2 (NRF2) 活性由辅因子调节,影响抗氧化反应元素 (ARE) 基因调节. 这种调节是特定于时间,化合物和暴露的,影响细胞平衡.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 核因素红色素2相关因子2 (NRF2) 调节抗氧化反应元素 (ARE) 基因,对细胞平衡至关重要.
- 规范NRF2计划灵活性及其下游目标监管的精确机制仍然不完全理解.
- Nrf2活动受到结合伙伴和辅助因子的影响,可能因应压力因素类型和非正规信号通路而有所不同.
研究的目的:
- 量化研究NRF2及其标基因硫胺1 (SRXN1) 之间的关系.
- 开发和应用数学模型来理解NRF2和SRXN1表达的动态.
- 阐明NRF2转录活动的特定条件调节机制.
主要方法:
- 开发了一个半机械的数学模型.
- 在HepG2细胞中分析了NRF2和SRXN1的时间过程蛋白质表达数据.
- 使用部分层次参数的非线性混合效应建模.
主要成果:
- 数学模型准确地捕获了实验NRF2和SRXN1表达动态.
- 对于NRF2的转录活动,它需要辅助因子或翻译后修改.
- 调节NRF2活动是特定于时间,化学化合物和暴露场景的.
结论:
- NRF2转录活性是通过辅因子或翻译后修改动态调节的.
- 了解NRF2介导的ARE基因激活需要对NRF2结合伙伴和辅助因子进行动态洞察.
- 本研究为剖析NRF2监管灵活性提供了定量框架.
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