Caspase involvement in RIP-associated CD95-induced T cell apoptosis
Caspase involvement in RIP-associated CD95-induced T cell apoptosis
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DOI：
10.1016/j.cellimm.2003.11.006
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发表时间：
2003-12-01
影响因子：
4.3
通讯作者：
McLeod, JD
中科院分区：
文献类型：
--
作者：
Bárcia, RN;Della Valle, NS;McLeod, JD
cd95诱导的细胞凋亡是T细胞的重要调控机制，目前认为这一复杂的信号通路包括蛋白激酶RIP。虽然RIP以其在TNF信号传导和NF-kappaB激活中的作用而闻名，但它包含一个死亡结构域，并且能够在切割时引起细胞凋亡。本研究探讨了RIP在cd95诱导的细胞凋亡中的作用及其与caspase级联反应的相互关系。研究在RIP-/- T细胞系和外周T淋巴细胞上进行，其中RIP通过添加格尔达霉素降解。细胞膜CD95-L诱导细胞凋亡，被认为是CD95-L生理上最相关的形式。结果显示RIP-/-细胞对死亡的易感性降低，从而证实了RIP在cd95诱导的细胞凋亡中的作用。此外，我们证实RIP在CD95-L刺激下被切割，这一过程可以被Z-VAD抑制。然而，只观察到Z-VAD对外周T淋巴细胞的部分抑制作用，这表明RIP可能不依赖于caspase。对效应caspase 3和启动caspase 2、8和9活性的研究表明，在没有RIP的情况下，这些caspase的活性降低，表明RIP相关的凋亡是caspase依赖的。因此，这些研究支持RIP在cd95诱导的T细胞凋亡中与caspase相关的作用。(C) 2003 Elsevier Inc.版权所有。
CD95-induced apoptosis is an important regulatory mechanism in T cells and this complex signalling pathway is now thought to include the protein kinase RIP. Although, RIP is best known for its role in TNF signalling and NF-kappaB activation, it contains a death domain and it is capable of causing apoptosis upon cleavage. In the present study, the role of RIP in CD95-induced apoptosis and its inter-relationship with the caspase cascade was investigated. Studies were performed on both a RIP-/- T cell line and peripheral T lymphocytes, where RIP was degraded through the addition of geldanamycin. Apoptosis was induced by membrane CD95-L, thought to be the most physiological relevant form of CD95-L. Results showed that RIP-/- cells had a decreased susceptibility to death, thus confirming a role for RIP in CD95-induced apoptosis. Furthermore, it was confirmed that RIP is cleaved upon CD95-L stimulation, a process that can be inhibited by Z-VAD. However, only partial inhibition in peripheral T lymphocytes by Z-VAD was observed, suggesting a potential caspase-independent processing of RIP. Studies performed on the activity of effector caspase 3 and on the initiator caspases 2, 8, and 9 revealed that, in the absence of RIP, the activity of these caspases decreases, indicating that RIP-associated apoptosis is caspase-dependent. Hence, these studies support a caspase-related role for RIP in CD95-induced T apoptosis. (C) 2003 Elsevier Inc. All rights reserved.