删除活性蛋白-1转录因子 JunD 诱导氧化应激并加速与年龄相关的内皮功能障碍
Francesco Paneni1, Elena Osto, Sarah Costantino
1Cardiology and Cardiovascular Research, Institute of Physiology and University Hospital, Zürich, Switzerland.
Circulation
|February 16, 2013
概括
JunD转录因子通过维持活性氧物种平衡来保护血管衰老. 失去JunD会加速衰老,而过度表达会防止与年龄相关的内皮功能障碍.
科学领域:
- 血管生物学 血管生物学
- 衰老研究研究 衰老研究
- 氧化压力是一种氧化压力.
背景情况:
- 反应性氧物种 (ROS) 显著影响血管衰老.
- 转录因子JunD因其对抗氧化应激的作用而得到认可.
- JunD在血管ROS稳态中的特定功能以前是未确定的.
研究的目的:
- 调查JunD在老化期间维持血管健康中的作用.
- 阐明JunD影响血管系统中反应性氧物种平衡的机制.
- 为了确定JunD是否可以成为与年龄相关的血管功能障碍的治疗标.
主要方法:
- 使用了各种年龄段的JunD淘汰 (JunD(-/-)) 和野生类型小鼠.
- 评估了内皮功能,氧化生产和氧化应激标志物.
- 分析了抗氧化酶,NADPH氧化酶子单元和衰老标记物的表达.
- 在老年小鼠和人类内皮细胞中研究了JUND调节.
主要成果:
- JunD(-/-) 小鼠表现出血管松功能受损,氧化生物可用性降低,氧化应激增加.
- 野生型小鼠的血管衰老与JunD表达和活性降低有关.
- JunD 过度表达可以防止因年龄引起的内皮功能障碍.
- 人类细胞中的JunD敲击模仿了在衰老中看到的氧化失衡.
结论:
- JunD对与衰老相关的内皮功能障碍起着关键的保护作用.
- JunD对于维持血管系统中反应性氧物种恒温是必不可少的.
- 准JUND可能提供一种新的策略来对抗ROS驱动的血管衰老.
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