A distinct pathway of cell-mediated apoptosis initiated by granulysin
A distinct pathway of cell-mediated apoptosis initiated by granulysin
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DOI：
10.4049/jimmunol.167.1.350
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发表时间：
2001-07-01
影响因子：
4.4
通讯作者：
Krensky, AM
中科院分区：
文献类型：
--
作者：
Kaspar, AA;Okada, S;Krensky, AM
颗粒溶素是一种表达于CTL和NK细胞颗粒中的抗微生物和杀肿瘤分子。在这项研究中，我们表明，颗粒溶解素破坏细胞膜上的负电荷，破坏线粒体的跨膜电位（Δ psi），并导致细胞色素c的释放。颗粒溶素诱导的细胞凋亡在过表达Bcl-2的细胞中被阻断。尽管释放细胞色素c，但procaspase 9不被加工。然而，在颗粒溶素处理的细胞中观察到半胱天冬酶3的激活，表明颗粒溶素激活不同于颗粒酶和死亡受体诱导的细胞凋亡的CTL和NK细胞介导的死亡的新途径。
Granulysin is an antimicrobial and tumoricidal molecule expressed in granules of CTL and NK cells. In this study, we show that granulysin damages cell membranes based upon negative charge, disrupts the transmembrane potential (Delta psi) in mitochondria, and causes release of cytochrome c. Granulysin-induced apoptosis is blocked in cells overexpressing Bcl-2. Despite the release of cytochrome c, procaspase 9 is not processed. Nevertheless, activation of caspase 3 is observed in granulysin-treated cells, suggesting that granulysin activates a novel pathway of CTL- and NK cell-mediated death distinct from granzyme- and death receptor-induced apoptosis.