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流式细胞术在分析线粒体细胞死亡中的应用

[The use of flow cytometry for analysis of the mitochondrial cell death].

作者信息

Pekarčíková L, Knopfová L, Ondroušková E, Smarda J

出版信息

Klin Onkol. 2014;27 Suppl 1:S15-21. doi: 10.14735/amko20141s15.

DOI:10.14735/amko20141s15
PMID:24945532
Abstract

Apoptosis is type I programmed cell death, a process that is essential for development and tissue homeostasis. It is a prevalent form of cell death and it proceeds via two signaling pathways - external (receptor pathway) triggered by death receptors and intrinsic (mitochondrial) apoptotic pathway with major involvement of mitochondria. Mitochondria are important cellular organelles producing energy stored in molecules of adenosine triphosphate that are essential for cell survival. The mitochondrial cell death is characterized by permeabilization of the mitochondrial outer membrane and dissipation of the transmembrane potential. Mitochondria are electronegative organelles and depolarization of the mitochondrial membrane is important for the release of proapoptotic signals. Aberrant control of the mitochondrial cell death might contribute to several diseases including cancer. Mitochondria are also a source of reactive oxygen species, Ca2+ ions and other proteins that affect processes important for the initiation and progression of tumors independently of apoptosis. Current studies focus on research of mitochondrial membrane potential and reactive oxygen species modulating various signaling pathways within the cell, their importance in carcinogenesis, and in treatment of oncological patients. Monitoring of the apoptotic markers, such as the mitochondrial membrane potential (MMP), and the level of reactive oxygen species in samples of oncological patients has a predictive value for the output of treatment protocols.

摘要

细胞凋亡是I型程序性细胞死亡,这一过程对发育和组织稳态至关重要。它是一种普遍的细胞死亡形式,通过两条信号通路进行——由死亡受体触发的外部(受体通路)和主要涉及线粒体的内在(线粒体)凋亡通路。线粒体是重要的细胞器,可产生储存于三磷酸腺苷分子中的能量,而三磷酸腺苷对细胞存活至关重要。线粒体细胞死亡的特征是线粒体外膜通透性增加和跨膜电位消散。线粒体是带负电的细胞器,线粒体膜去极化对于促凋亡信号的释放很重要。线粒体细胞死亡的异常调控可能导致包括癌症在内的多种疾病。线粒体也是活性氧、钙离子和其他蛋白质的来源,这些物质独立于细胞凋亡影响肿瘤发生和发展过程中重要的过程。当前的研究集中在线粒体膜电位和活性氧对细胞内各种信号通路的调节、它们在致癌作用中的重要性以及在肿瘤患者治疗中的作用。监测肿瘤患者样本中的凋亡标志物,如线粒体膜电位(MMP)和活性氧水平,对治疗方案的疗效具有预测价值。

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