Involvement of 5-lipoxygenase in survival of Epstein-Barr virus (EBV)-converted B lymphoma cells
Involvement of 5-lipoxygenase in survival of Epstein-Barr virus (EBV)-converted B lymphoma cells
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DOI：
10.1016/j.canlet.2007.03.010
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发表时间：
2007-09-08
期刊：
影响因子：
9.7
通讯作者：
Gualandi, Giamplero
中科院分区：
文献类型：
--
作者：
Belfiore, Maria Cristina;Natoni, Alessandro;Gualandi, Giamplero
EB病毒（EBV）通过尚不清楚的机制参与淋巴瘤的进展，该机制涉及对诱导的细胞凋亡的抗性增加。我们在这里表明，在一组抗肿瘤EBV转化的伯基特淋巴瘤克隆，5-和12-脂氧合酶（LOX）过度表达。对5-LOX的进一步研究表明，对凋亡的抵抗性与5-脂氧合酶（5-LOX）的表达平行增加。5-LOX抑制剂：（a）降低过氧化物水平，表明该酶促进EBV+细胞中氧化应激的产生，和（B）在EBV抗性细胞系E2 R中有效诱导细胞凋亡。5-和15-HETE，5和15-LOX的产物，分别抵消5-LOX抑制剂诱导的细胞凋亡，表明花生四烯酸代谢的产物，而不是过氧化物，触发EBV转化的细胞存活所需的信号转导。这些发现表明，5-和，在较小程度上，其他LOX，参与肿瘤进展的几种细胞类型，也可能参与淋巴瘤，特别是EBV介导的。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Epstein-Barr Virus (EBV) is involved in the progression of lymphomas through still unknown mechanism involving increased resistance to induced apoptosis. We show here that in a set of apoptosis-resistant EBV-converted Burkitt's lymphoma clones, 5- and 12-lipoxygenases (LOXs) are over-expressed. Further investigations on 5-LOX showed that resistance to apoptosis increases parallely with the expression of 5-lipoxygenase (5-LOX). Inhibitors of 5-LOX: (a) decrease peroxides level, indicating that this enzyme promotes the generation of oxidative stress in EBV+ cells, and (b) potently induce apoptosis in the EBV resistant cell line E2R. 5- and 15-HETE, the products of the 5 and 15-LOXs, respectively, counteract 5-LOX inhibitor induced apoptosis, indicating that products of arachidonate metabolism, rather than peroxides, trigger a signal transduction that is required for survival of the EBV-converted cells. These findings suggest that 5- and, to a lesser extent, other LOXs, that are involved in tumor progression of several cell types, may also participate in lymphomagenesis, especially that EBV-mediated. (c) 2007 Elsevier Ireland Ltd. All rights reserved.