ATF5调节的线粒体展开蛋白反应通过线粒体ROS减少内分泌网膜应激,减轻性大鼠的神经损伤
Xiaolei Lian1,2, Xiaoyi Wang3, Yinyin Xie1
1Department of Neurology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, Henan, China.
Neurochemical research
|October 17, 2023
概括
激活转录因子5 (ATF5) 通过增强线粒体功能和减少内质网膜 (ER) 压力来保护抗发作. 这项研究表明,ATF5调节的线粒体未折叠蛋白反应 (mtUPR) 在模型中具有神经保护作用.
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
- 分子生物学分子生物学
背景情况:
- 细胞内膜网膜 (ER) 的压力有助于在发作期间的神经元损伤.
- 线粒体反应性氧物种 (ROS) 与ER压力有关,激活转录因子5 (ATF5) 调节线粒体未折叠蛋白反应 (mtUPR).
- 在相关的ER压力和神经元损伤中,ATF5调节的mtUPR的确切作用尚不清楚.
研究的目的:
- 为了研究ATF5调节的mtUPR在皮洛卡尔诱导的老鼠模型中的神经保护作用.
- 阐明涉及ER压力和线粒体ROS的潜在机制.
主要方法:
- 使用了一种由皮洛卡尔诱导的的老鼠模型.
- 使用lentivirus感染 (上调和下调) 操纵ATF5表达.
- 评估了神经元损伤,细胞亡,ER压力标志物 (GRP78,PERK,ATF4,CHOP),mtUPR组件 (HSP60,ClpP),线粒体ROS水平,以及与细胞亡相关的蛋白质 (BCL2,BAX,分裂-卡斯帕酶-3).
- 用抗氧化剂mito-TEMPO来评估其保护作用.
主要成果:
- ATF5上调减轻了发作引起的神经元损伤和亡,而下调加剧了这些影响.
- ATF5上调增强了mtUPR,减少了线粒体ROS,并抑制了ER压力标志物.
- 在ATF5上调调节下降了亲亡蛋白 (BAX,分裂-caspase-3) 和增加了抗亡蛋白 (BCL2).
- 通过减少线粒体ROS,Mito-TEMPO减轻了ATF5下调的有害影响.
结论:
- 在模型中,ATF5调节的mtUPR对发作具有显著的神经保护作用.
- 保护机制包括减少线粒体ROS,从而减轻ER压力和神经元亡.
- 向ATF5-介导的mtUPR代表了的潜在治疗策略.
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