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4'-氯地西泮保护T98G星形胶质细胞系中的线粒体免受葡萄糖剥夺的影响。

4'-Chlorodiazepam Protects Mitochondria in T98G Astrocyte Cell Line from Glucose Deprivation.

作者信息

Baez Eliana, Guio-Vega Gina Paola, Echeverria Valentina, Sandoval-Rueda Daniel Andres, Barreto George E

机构信息

Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia.

Universidad San Sebastián, Lientur 1457, 4030000, Concepción, Chile.

出版信息

Neurotox Res. 2017 Aug;32(2):163-171. doi: 10.1007/s12640-017-9733-x. Epub 2017 Apr 13.

DOI:10.1007/s12640-017-9733-x
PMID:28405935
Abstract

The translocator protein (TSPO), formerly known as the peripheral-type benzodiazepine receptor (PBR), is considered an important regulator of steroidogenesis and a potential therapeutic target in neurological disorders. Previous evidence suggests that TSPO ligands can protect cells during injury and prevent apoptosis in central nervous system (CNS) cells. However, its actions on astrocytic cells under metabolic injury are not well understood. In this study, we explored whether 4'-chlorodiazepam (Ro5-4864), a TSPO ligand, might protect astrocyte mitochondria under glucose deprivation. Our results showed that 4'-chlorodiazepam preserved cell viability and reduced nuclear fragmentation in glucose-deprived cells. These effects were accompanied by a reduced production of free radicals and maintenance of mitochondrial functions in cells treated with 4'-chlorodiazepam. Finally, our findings suggest that TSPO might be involved in reducing oxidative stress by preserving mitochondrial functions in astrocytic cells exposed to glucose withdrawal.

摘要

转位蛋白(TSPO),以前称为外周型苯二氮䓬受体(PBR),被认为是类固醇生成的重要调节因子以及神经疾病的潜在治疗靶点。先前的证据表明,TSPO配体可在损伤期间保护细胞,并防止中枢神经系统(CNS)细胞凋亡。然而,其在代谢性损伤下对星形胶质细胞的作用尚不清楚。在本研究中,我们探究了TSPO配体4'-氯地西泮(Ro5-4864)是否可能在葡萄糖剥夺情况下保护星形胶质细胞的线粒体。我们的结果表明,4'-氯地西泮可维持细胞活力并减少葡萄糖剥夺细胞中的核碎裂。这些作用伴随着4'-氯地西泮处理的细胞中自由基产生减少以及线粒体功能的维持。最后,我们的研究结果表明,TSPO可能通过维持暴露于葡萄糖剥夺的星形胶质细胞中的线粒体功能来参与减轻氧化应激。

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本文引用的文献

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Combined PET Imaging of the Inflammatory Tumor Microenvironment Identifies Margins of Unique Radiotracer Uptake.联合 PET 成像炎症肿瘤微环境识别独特放射性示踪剂摄取的边界。
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Translational evaluation of translocator protein as a marker of neuroinflammation in schizophrenia.
TSPO 在 线粒体生物能量学和免疫过程中的作用。
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Psychiatric drugs impact mitochondrial function in brain and other tissues.精神科药物会影响大脑和其他组织中的线粒体功能。
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TSPO Ligands Promote Cholesterol Efflux and Suppress Oxidative Stress and Inflammation in Choroidal Endothelial Cells.TSPO 配体促进脉络膜内皮细胞胆固醇外流,抑制氧化应激和炎症。
Int J Mol Sci. 2018 Nov 24;19(12):3740. doi: 10.3390/ijms19123740.
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Role of GTPases in the Regulation of Mitochondrial Dynamics in Alzheimer's Disease and CNS-Related Disorders.GTPases 在阿尔茨海默病和中枢神经系统相关疾病中线粒体动力学调节中的作用。
Mol Neurobiol. 2019 Jun;56(6):4530-4538. doi: 10.1007/s12035-018-1397-x. Epub 2018 Oct 18.
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Metabolic Abnormalities of Erythrocytes as a Risk Factor for Alzheimer's Disease.红细胞代谢异常作为阿尔茨海默病的一个风险因素
Front Neurosci. 2018 Jan 5;11:728. doi: 10.3389/fnins.2017.00728. eCollection 2017.
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Reconceptualization of translocator protein as a biomarker of neuroinflammation in psychiatry.重新将 translocator protein 概念化为精神病学中神经炎症的生物标志物。
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