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通过线粒体转位蛋白18kDaDa调节天体细胞代谢
Wyn Firth1, Josephine L Robb1, Daisy Stewart1
1University of Exeter Medical School, Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
bioRxiv : the preprint server for biology
|October 24, 2023
概括
线粒体转位蛋白18kDa (TSPO) 调节天体细胞的代谢灵活性,影响呼吸和脂肪酸氧化. 在这项研究中,TSPO的损失并没有改变星球细胞的炎症反应.
科学领域:
- 神经科学是一个神经科学.
- 细胞的新陈代谢
- 神经炎症是一种神经炎症.
背景情况:
- 线粒体转位蛋白18kDa (TSPO) 与各种细胞功能有关,是中枢神经系统 (CNS) 炎症的治疗点.
- TSPO在星球细胞中的作用对大脑恒温至关重要,尚未得到充分研究,特别是其对星球细胞代谢和免疫代谢过程的影响.
- 在炎症期间,TSPO表达在星球细胞中增加,可能导致反应性.
研究的目的:
- 研究TSPO在调节天体细胞代谢和免疫代谢反应中的作用.
- 为了确定TSPO缺乏是否影响天体细胞的代谢灵活性和炎症信号.
主要方法:
- 对 TSPO 缺乏 (TSPO-/-) 的小鼠初级星球细胞 (MPA) 和 U373 人类星球细胞瘤细胞进行了代谢流量分析.
- 同免疫沉被用来识别U373细胞中TSPO相互作用的蛋白质.
- 在TSPO-/-中评估了用脂多糖 (LPS) 刺激的MPA的炎症反应.
主要成果:
- 失去TSPO减少了基底星细胞呼吸和乳酸生产,同时增加了脂肪酸氧化 (FAO) 和对重新引入葡萄糖的生物能量反应.
- 发现TSPO与carnalitine palmitoyltransferase 1a形成一个复合体,这表明了TSPO介导的粮农组织调节机制.
- 在LPS刺激时,TSPO缺乏减弱了早期 (3小时) 瘤亡因子的释放,但在以后的时间点 (24小时) 增强了它.
结论:
- TSPO 作为天体细胞代谢灵活性的调节者.
- 在使用的实验条件下,TSPO的损失似乎没有显著调节星球细胞对炎症的整体代谢反应.
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