Cell death induced by granzyme C
Cell death induced by granzyme C
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DOI：
10.1182/blood-2002-08-2485
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发表时间：
2003-04-15
期刊：
影响因子：
20.3
通讯作者：
Ley, TJ
中科院分区：
文献类型：
--
作者：
Johnson, H;Scorrano, L;Ley, TJ
虽然颗粒酶A和B的功能已经被定义，但小鼠细胞毒性淋巴细胞(C、D和F)的其他高表达颗粒酶(GZM)的功能还没有被评估。在这份报告中，我们描述了小鼠GzmC(与人类Geanzyme H关系最密切)导致细胞死亡的能力。诱导死亡需要其蛋白水解酶的活性，其特征是。通过磷脂酰丝氨酸的快速外化，核的凝聚和崩塌，以及单链DNA划痕。这些事件的动力学类似于颗粒酶B引起的事件，其效力(以摩尔为基础定义)也是相同的。死亡的诱导不涉及caspase的激活、Bid的切割或CAD核酸酶的激活。然而，颗粒酶C确实引起完整细胞或分离线粒体的快速肿胀和去极化，这种线粒体损伤不能被环孢菌素A预防。这些结果表明，颗粒酶C通过攻击核靶和线粒体靶而迅速诱导靶细胞死亡，这些TAR不同于颗粒酶B用来引起经典细胞凋亡的那些。(C)2003年，由美国血液病学会提供。
Although the functions of granzymei A and B have been defined, the functions of the other highly expressed granzymes (Gzms) of murine cytotoxic lymphocytes (C, D, and F) have not yet been evaluated. In this report, we describe the ability of murine GzmC (which is most closely related to human geanzyme H) to cause cell death. The induction of death requires its protease activity and is characterized. by the rapid externalization of phospoatidyl-serine, nuclear condensation and collapse, and single-stranded DNA nicking. The kinetics of these events are similar to those caused by granzyme B, and its potency (defined on molar basis) is also equivalent. The induction of death did not involve the activation of caspases, the cleavage of BID, or the activation of the CAD nuclease. However, granzyme C did cause rapid mitochondrial swelling and depolarization in intact cells or in isolated mitochondria, and this mitochondrial damage was not prevented by cycldsporin A pretreatment. These results suggest that granzyme C rapidly induces target cell death by attacking nuclear and mitochondrial targets and that these tar gets are distinct from those, used by granzyme B to cause classical apoptosis. (C) 2003 by The American Society of Hematology.