G-CSF重塑了细胞质PCNA支架,并调节了中性粒细胞中的糖解
Karen Aymonnier1, Enzo Bosetta1, Nathan G F Leborgne1
1Department of Immunology, Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Université Paris Cité, 27 rue du faubourg Saint Jacques, Paris F-75014, France.
Journal of leukocyte biology
|October 12, 2023
概括
颗粒细胞殖民地刺激因子 (G-CSF) 改变了增殖细胞核抗原 (PCNA) 与中性粒细胞中的糖解酶相互作用的方式,影响了炎症期间的能量代谢. 这种G-CSF诱导的PCNA功能重编程对于在炎症和瘤环境中的中性粒细胞行为至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 代谢过程中的代谢.
背景情况:
- 细胞增殖细胞核抗原 (PCNA) 是一个关键的支架蛋白调节中性粒细胞的生存和功能.
- 在恒温条件下的中性粒细胞中PCNA互动组已知,但其在炎症等病理生理状态中的作用不太清楚.
- 颗粒细胞殖民地刺激因子 (G-CSF) 是一种关键的细胞因子,在炎症反应期间影响中性粒细胞生物学.
研究的目的:
- 为了研究PCNA在接受G-CSF治疗的捐赠者的中性粒细胞中的作用和相互作用,作为炎症的模型.
- 了解G-CSF如何影响PCNA与代谢酶的相互作用,特别是糖解中的酶.
- 阐明改变PCNA-糖解相互作用对中性粒细胞代谢和行为的功能后果.
主要方法:
- 从接受G-CSF治疗的捐赠者 (GDs) 和健康的捐赠者 (HDs) 中,对中性粒细胞的蛋白质组学分析.
- 在GDs与HDs中PCNA互动组的表征.
- 评估中性粒细胞糖解和p21竞争对手对PCNA糖解调节的影响.
主要成果:
- 在GD中性粒细胞中,PCNA显著上调,与HDs相比,PCNA互动组具有明显的PCNA互动组.
- 在GD中,PCNA与糖分酶的关联性下降,与增加的中性粒细胞糖解相关.
- 在HD中性粒细胞中,PCNA负调节了糖解,但在GD中性粒细胞中,这种效应被废除了.
结论:
- G-CSF改变了PCNA支架,修改了它与糖溶酶的相互作用,从而调节了中性粒细胞糖解.
- PCNA对糖解的选择性控制是组织中性粒细胞功能的一种机制,补充了其在延长生存中的作用.
- 在炎症或瘤环境中,PCNA在中性粒细胞的代谢重编程中发挥着重要作用.
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