硫酸硫酸硫转移酶缺乏促进氧化应激和异常NRF2功能在大脑中
Yang Luo1, Laurent Chatre2, Shaden Melhem3
1University of Groningen, Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, Groningen, the Netherlands; University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands.
Redox biology
|November 24, 2023
概括
硫酸硫酸转化酶 (TST) 缺乏会损害大脑的氧化还原平衡,并增加神经元对氧化应激的敏感性. TST损失改变了反应性氧和硫物种,影响了线粒体功能和抗氧化防御.
科学领域:
- 生物化学 生物化学
- 神经科学是一个神经科学.
- 线粒体生物学 线粒体生物学
背景情况:
- 硫酸硫酸盐硫转移酶 (TST) 已知用于化物排毒以及硫化代谢和抗氧化剂防御中的作用.
- 虽然TST的功能已经在肝脏和结肠中确立,但它在大脑中的作用在很大程度上是未知的.
- 了解TST的大脑功能对于解决与氧化应激相关的神经疾病至关重要.
研究的目的:
- 在TST缺陷的小鼠模型 (Tst-/-小鼠) 中研究TST在维持大脑氧化还原平衡中的作用.
- 描述大脑中TST损失的生物化学表型,重点关注神经元活动和氧化应激敏感性.
- 阐明TST缺乏对反应性物种代谢和大脑中的线粒体功能的影响.
主要方法:
- 使用了全球TST缺陷的小鼠模型 (Tst-/-) 和野生类型控制 (C57BL/6J).
- 分析了大脑皮层的反应性氧物种 (ROS) 和反应性硫物种 (RSS) 的变化,包括多硫化物.
- 评估了线粒体氧化酸化 (OXPHOS) 改造,Nrf2-Keap1通路和依赖醇的抗氧化功能.
- 在帕拉克瓦特诱导的氧化应激后评估的抗氧化能力.
主要成果:
- 由于改变了ROS和聚硫化物生成,TST缺陷扰乱了大脑皮层中的反应性物种相互作用体.
- 在Tst-/-小鼠中观察到线粒体OXPHOS重塑和异常Nrf2-Keap1表达.
- 硫醇依赖的抗氧化功能受到损害,导致氧化应激下抗氧化能力降低.
- 与对照组相比,Tst-/-小鼠对帕拉克瓦特诱导的氧化损伤的敏感性增加.
结论:
- 通过改变反应性物种代谢和线粒体功能,TST缺乏会显著影响大脑的氧化还原平衡.
- 失去TST功能使神经元更容易受到与氧化压力相关的损伤.
- 这些发现凸显了TST在大脑健康中的关键作用,并表明了涉及氧化应激的神经障碍的潜在治疗点.
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