18kDa转位蛋白TSPO 是星球细胞反应活性的调解者
Benjamin B Tournier1,2, Farha Bouteldja2, Quentin Amossé2
1Department of Psychiatry, University Hospitals of Geneva, Geneva 1206, Switzerland.
ACS omega
|September 4, 2023
概括
在阿尔茨海默病中常见的反应性星球细胞中增加的转位蛋白 (TSPO) 促进炎症并改变葡萄糖代谢. 针对TSPO可能通过减轻这些有害影响来提供治疗益处.
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
- 免疫学 免疫学 免疫学
背景情况:
- 在阿尔茨海默氏症 (AD) 中观察到星球细胞的反应性和转位蛋白 (TSPO) 密度的增加,这与促进炎症的环境有关.
- TSPO在星球细胞功能中的确切作用及其对AD病原体的贡献仍然不清楚.
研究的目的:
- 在炎症条件下阐明驱动TSPO在天体细胞上调调节的机制.
- 研究TSPO表达增加对天体细胞代谢和炎症反应的功能后果.
主要方法:
- 使用C6星系细胞系,用脂聚糖化物 (LPS) 处理或因TSPO过度表达而转染.
- 评估TSPO表达,线粒体含量,活性氧物种 (ROS) 生产和葡萄糖吸收 (FDG).
- 研究了一种TSPO抗剂 (FEPPA) 和STAT3信号通路的影响.
主要成果:
- 通过STAT3依赖的途径,LPS诱导TSPO表达,增加线粒体和ROS产量,同时降低葡萄糖吸收.
- 单单过度表达TSPO就会增加ROS的产生,而FEPPA则可以逆转这种效应.
- 过度表达LPS和TSPO对ROS产生产生了协同效应.
- FEPPA减轻了LPS诱导的ROS产生和减少了葡萄糖消耗.
结论:
- 星球细胞中高调 TSPO 有助于调节葡萄糖代谢,并加剧促炎反应.
- 这些发现表明,在AD期间天体细胞中TSPO升高可能会通过促进炎症而有害.
相关概念视频
Translocation of Proteins into the Mitochondria
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Energy to Drive Translocation
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
Protein Transport to the Stroma
Chloroplasts are triple membrane structures with an outer membrane, an inner membrane, and a thylakoid membrane, each containing distinct metabolite transporters, membrane translocons, and enzymes. Appropriate sorting and translocating these proteins to their correct membrane systems is essential for chloroplast function.
Protein complexes called the translocon of the outer chloroplast membrane or TOC complex, and the translocon of the inner chloroplast membrane or TIC complex mediate the...
Protein complexes called the translocon of the outer chloroplast membrane or TOC complex, and the translocon of the inner chloroplast membrane or TIC complex mediate the...
Cotranslational Protein Translocation
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Protein Transport to the Thylakoids
Thylakoids are membrane-bound sac-like structures within the chloroplast that serve as sites for photosynthesis. Thylakoid lumen contains many electron transport proteins and is enclosed by a thylakoid membrane rich in the light-harvesting complex. Proteins targeted to the thylakoids are transported as precursors and are sorted by the general TOC/TIC import pathway. Once the precursor reaches the stroma, stromal processing peptidases remove their transit signal and expose thylakoid signal...

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