The antitumor ether lipid ET-18-OCH3 induces apoptosis through translocation and capping of Fas/CD95 into membrane rafts in human leukemic cells
The antitumor ether lipid ET-18-OCH3 induces apoptosis through translocation and capping of Fas/CD95 into membrane rafts in human leukemic cells
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DOI：
10.1182/blood.v98.13.3860
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发表时间：
2001-12-15
期刊：
影响因子：
20.3
通讯作者：
Mollinedo, F
中科院分区：
文献类型：
--
作者：
Gajate, C;Mollinedo, F
抗肿瘤醚脂ET-18-OCH3通过激活细胞内Fas/CD95促进肿瘤细胞的凋亡。本研究结果表明，ET-18-OCH3在人白血病细胞发生凋亡前，可诱导Fas和膜筏共帽，Fas和膜筏是参与信号转导的特殊质膜区域。在ET-18-OCH3处理的白血病细胞中，成片的膜筏聚集了Fas簇。T-白血病Jurkat细胞经ET-18-OCH3处理后，Triton X-100细胞裂解物蔗糖梯度离心法显示Fas移位到膜筏中。甲基-β-环糊精或非利平破坏膜筏完整性可抑制ET-18-OCH3诱导的白血病原代细胞和细胞系的凋亡。甲基-β-环糊精也能抑制Fas的聚集。这些数据表明，ET-18-OCH3重组膜筏以触发人白血病细胞的凋亡，而ET-18-OCH3诱导的凋亡需要Fas与膜筏共聚集。Fas的这种移位到膜筏中，可能为通过膜微区重组而放大Fas信号提供了一种机制。(C)2001年，由美国血液病学会提供。
The antitumor ether lipid ET-18-OCH3 promotes apoptosis in tumor cells through intracellular activation of Fas/CD95. Results of this study showed that ET-18-OCH3 induces cocapping of Fas and membrane rafts, specialized plasma membrane regions involved in signaling, before the onset of apoptosis in human leukemic cells. Patches of membrane rafts accumulated Fas clusters in leukemic cells treated with ET-18-OCH3. Sucrose gradient centrifugation of Triton X-100 cell lysates showed that Fas translocated into membrane rafts following ET-18-OCH3 treatment of T-leukemic Jurkat cells. Disruption of membrane raft integrity by methyl-beta -cyclodextrin or filipin inhibited ET-18-OCH3-induced apoptosis in leukemic primary cells and cell lines. Fas clustering was also inhibited by methyl-beta -cyclodextrin. These data indicate that ET-18-OCH3 reorganizes membrane rafts to trigger apoptosis In human leukemic cells, and that Fas coaggregation with membrane rafts Is required for ET-18-OCH3-induced apoptosis. This translocation of Fas into membrane rafts may provide a mechanism for amplifying Fas signaling by reorganization of membrane microdomains. (C) 2001 by The American Society of Hematology.