Rapid extracellular release of cytochrome c is specific for apoptosis and marks cell death in vivo
Rapid extracellular release of cytochrome c is specific for apoptosis and marks cell death in vivo
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DOI：
10.1182/blood.v98.5.1542
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发表时间：
2001-09-01
期刊：
影响因子：
20.3
通讯作者：
Los, M
中科院分区：
文献类型：
--
作者：
Renz, A;Berdel, WE;Los, M
包括抗癌药物在内的各种死亡刺激通过诱导细胞色素c从外线粒体移位到胞浆中来触发细胞凋亡。一旦释放，细胞色素c与凋亡蛋白激活因子-1和脱氧腺苷三磷酸协同作用，激活caspase-9，启动凋亡蛋白酶级联反应。本研究结果表明，在化疗药物、星形孢子素诱导死亡和触发死亡受体CD95后，细胞色素c不仅移位到胞浆内，而且在胞外培养上清液中也能大量检测到细胞色素c。细胞色素c的释放是一种快速的、特定于细胞凋亡的过程，发生在诱导细胞凋亡后的1小时内，而不是在坏死期。有趣的是，血液系统恶性肿瘤患者的血清中细胞色素c水平升高。在癌症化疗过程中，由于细胞死亡增加，大多数患者的血清细胞色素c水平迅速上升。这些数据表明，监测肿瘤患者血清中的细胞色素c可能是一种有用的临床标志物，可用于检测体内细胞凋亡和细胞周转的开始。(C)2001年，由美国血液病学会提供。
Diverse death stimuli including anticancer drugs trigger apoptosis by inducing the translocation of cytochrome c from the outer mitochondrial compartment into the cytosol. Once released, cytochrome c cooperates with apoptotic protease-activating factor-1 and deoxyadenosine triphosphate in caspase-9 activation and initiation of the apoptotic protease cascade. The results of this study show that on death induction by chemotherapeutic drugs, staurosporine and triggering of the death receptor CD95, cytochrome c not only translocates into the cytosol, but furthermore can be abundantly detected in the extracellular medium. The cytochrome c release from the cell Is a rapid and apoptosis-specific process that occurred within 1 hour after induction of apoptosis, but not during necrosis. Interestingly, elevated cytochrome c levels were observed in sera from patients with hematologic malignancies. In the course of cancer chemo-therapy, the serum levels of cytochrome c in the majority of the patients grew rapidly as a result of increased cell death. These data suggest that monitoring of cytochrome c In the serum of patients with tumors might serve as a useful clinical marker for the detection of the onset of apoptosis and cell turnover in vivo. (C) 2001 by The American Society of Hematology.