TSPO deficiency induces mitochondrial dysfunction, leading to hypoxia, angiogenesis and a growth-promoting metabolic shift towards glycolysis in glioblastoma.
TSPO 缺乏诱导线粒体功能障碍,导致缺氧、血管生成和胶质母细胞瘤向糖酵解的促生长代谢转变。
TSPO angiogenesis glioma glycolysis mitochondrial oxidative phosphorylation
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摘要

BACKGROUND:The ligands of mitochondrial translocator protein (TSPO) have been widely used as diagnostic biomarkers for glioma. However, the true biological actions of TSPO in vivo and its role in glioma tumourigenesis remain elusive.
METHODS:TSPO knockout xenograft and spontaneous mouse glioma models were employed to assess the roles of TSPO in the pathogenesis of glioma. A Seahorse Extracellular Flux Analyzer was used to evaluate mitochondrial oxidative phosphorylation and glycolysis in TSPO knockout and wild-type glioma cells.
RESULTS:TSPO deficiency promoted glioma cell proliferation in vitro in mouse GL261 cells and patient-derived stem cell-like GBM1B cells. TSPO knockout increased glioma growth and angiogenesis in intracranial xenografts and a mouse spontaneous glioma model. Loss of TSPO resulted in a greater number of fragmented mitochondria, increased glucose uptake and lactic acid conversion, decreased oxidative phosphorylation and increased glycolysis.
CONCLUSION:TSPO serves as a key regulator of glioma growth and malignancy by controlling the metabolic balance between mitochondrial oxidative phosphorylation and glycolysis.

译文

背景: 线粒体转运蛋白 (TSPO) 的配体已被广泛用作胶质瘤的诊断生物标志物。然而,TSPO 在体内的真实生物学行为及其在胶质瘤肿瘤发生中的作用仍然难以捉摸。
方法: 采用 TSPO 敲除异种移植和自发性小鼠胶质瘤模型来评估 TSPO 在胶质瘤发病机制中的作用。海马细胞外通量分析仪用于评估 TSPO 敲除和野生型胶质瘤细胞线粒体氧化磷酸化和糖酵解。
结果: TSPO 缺乏促进了小鼠 GL261 细胞和病人来源的干细胞样 GBM1B 细胞在体外的胶质瘤细胞增殖。TSPO 敲除增加了颅内异种移植和小鼠自发性胶质瘤模型中的胶质瘤生长和血管生成。TSPO 的丢失导致更多的碎裂线粒体,增加葡萄糖摄取和乳酸转化,减少氧化磷酸化和增加糖酵解。
结论: TSPO 通过控制线粒体氧化磷酸化和糖酵解之间的代谢平衡,成为胶质瘤生长和恶性肿瘤的关键调节因子。

Glycolysis

内分泌 代谢途径 临床研究术语
概述  :  

糖酵解是代谢途径,在此过程中释放的自由能用于形成高能分子ATP(三磷酸腺苷)和NADH(还原烟酰胺腺嘌呤二核苷酸)。糖酵解是十个酶催化反应的序列,大多数单糖,例如果糖和半乳糖,可以转化为这些中间体之一。糖酵解是一种不依赖氧的代谢途径,糖酵解的广泛发生表明它是古老的代谢途径。在大多数生物中,糖酵解发生在细胞质中。反应过程糖酵解的第一步是通过称为己糖激酶的一系列酶将葡萄糖磷酸化,形成6-磷酸葡萄糖(G6P)。该反应消耗了ATP,但它的作用是使葡萄糖浓度保持在较低水平,从而促进葡萄糖通过质膜转运蛋

Glycolysis   英/glaɪ'kɒlɪsɪs/   美/glaɪ'kɑləsɪs/

释    义   n. 糖酵解

例    句   The principal metabolic pathway of RBC is glycolysis, and the main energy source in most species is glucose.红细胞的主要代谢途径是糖酵解,而大多数物种的主要能量来源是葡萄糖。

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