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囊氨酸β合成酶/H2S轴在老化大脑中的星细胞功能障碍中的作用

Anindya Dey¹, Pijush Kanti Pramanik¹, Shailendra Kumar Dhar Dwivedi²

¹Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.

|November 10, 2023

概括

囊氨酸β-合成酶 (CBS) 和硫化 (H2S) 保护天体细胞免受氧化应激. 在老年大脑中,这种CBS/H2S轴的下调会损害星细胞功能,增加神经退行风险.

科学领域:

神经科学是一个神经科学.
细胞生物学细胞生物学
生物化学生物化学

背景情况:

星细胞功能障碍是神经退行性疾病的关键因素.
驱动星细胞功能障碍的确切机制尚不清楚.
星球细胞表达cystathionineβ-synthase (CBS),这是一个参与硫化 (H2S) 生产的酶.

研究的目的:

调查CBS/H2S通路在天体细胞功能中的作用.
为了确定CBS枯竭和氧化应激对星球细胞的影响.
探索CBS/H2S轴作为老化大脑治疗点的潜力.

主要方法:

研究了小鼠和人类天体细胞中的CBS表达.
在星球细胞中利用了CBS的遗传枯竭.
评估了线粒体功能,反应性氧物种 (ROS) 生产和细胞生物能量学.
研究了外源H2S补充剂的影响.
在氧化应激条件下分析了蛋白质持续硫化水平.
研究了CBS/H2S轴在老化大脑组织中的活性.

主要成果:

在星球细胞中,CBS的表达很高.
天体细胞中CBS的枯竭导致线粒体功能障碍,ROS的增加和生物能量的减少.
外源的H2S或CBS再表达部分地挽救了这些赤字.
氧化应激会降低CBS/H2S轴,蛋白质持续硫化和天体细胞增殖.
老化的大脑表现出下调的CBS/H2S信号,加剧了氧化应激.
蛋白质化减少与衰老中的星球细胞功能受损有关.

结论:

在星球细胞中,CBS/H2S轴起着至关重要的保护作用.
这个轴的下调有助于氧化应激和老年大脑的功能障碍.
针对CBS/H2S通路可能为与年龄相关的神经退行性疾病提供治疗策略.

关键词:

衰老的衰老衰老的衰老星球细胞是星球细胞.硫化是一种硫化.氧化应激是一种氧化应激.蛋白质的持续硫化.

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