Hydroxyl radical-induced apoptosis in human tumor cells is associated with telomere shortening but not telomerase inhibition and caspase activation
Hydroxyl radical-induced apoptosis in human tumor cells is associated with telomere shortening but not telomerase inhibition and caspase activation
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DOI：
10.1016/s0014-5793(00)02377-2
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发表时间：
2001-01-19
期刊：
影响因子：
3.5
通讯作者：
Dai, YR
中科院分区：
文献类型：
--
作者：
Ren, JG;Xia, HL;Dai, YR
已经发现活性氧（ROS）触发肿瘤细胞的凋亡。同时，端粒酶被发现与恶性肿瘤和细胞凋亡减少有关，但对ROS如（OH）-O-之间的联系知之甚少。和端粒酶/端粒之间的相互关系。和端粒酶/端粒在肿瘤细胞杀伤中的作用，用（OH）-O-诱导HeLa、293和MW 451细胞发生凋亡。通过Fe 2+介导的芬顿反应（0.1 mM FeSO 4加0.3-0.9 mM H2 O2）产生的自由基和端粒酶活性，在细胞凋亡过程中测量端粒长度，我们发现在（OH）-O-.-期间诱导细胞凋亡，端粒缩短，而端粒酶活性无变化。我们的研究结果表明，（OH）-O-.-诱导的端粒缩短不是通过端粒酶抑制，而是（OH）-O-的直接作用。对端粒本身的影响，表明端粒缩短而不是端粒酶抑制是（OH）-O-.诱导细胞凋亡，我们还发现（OH）-O-.诱导的HeLa细胞凋亡不依赖于caspase-3，但与线粒体跨膜电位降低有关。结果表明，（OH）-O-.通过端粒相关的、半胱天冬酶非依赖性途径触发凋亡性肿瘤细胞死亡。(C)2001年欧洲生物化学学会联合会。由Elsevier Science B.V出版，保留所有权利。
Reactive oxygen species (ROS) have been found to trigger apoptosis in tumor cells. At the same time, telomerase is found to be associated with malignancy and reduced apoptosis, However little is known about the linkage between ROS such as (OH)-O-. and telomerase/telomere, To address the interrelations between (OH)-O-. and telomerase/telomere in tumor cell killing, HeLa, 293 and MW451 cells were induced to undergo apoptosis with (OH)-O-. radicals generated via Fe2+-mediated Fenton reactions (0.1 mM FeSO4 plus 0.3-0.9 mM H2O2) and telomerase activity, telomere length were measured during apoptosis, We found that during (OH)-O-.-induced apoptosis, telomere shortening took place while no changes in telomerase activity were observed. Our results suggest that (OH)-O-.-induced telomere shortening is not through telomerase inhibition but possibly a direct effect of (OH)-O-. on telomeres themselves indicating that telomere shortening but not telomerase inhibition is the primary event during (OH)-O-.-induced apoptosis, Strikingly, we also found that (OH)-O-.-induced apoptosis in HeLa cells is caspase-3-independent but is associated with reduction of mitochondrial transmembrane potential. Our results indicate that (OH)-O-. triggers apoptotic tumor cell death through a telomere-related, caspase-independent pathway. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V, All rights reserved.