Hydroxyl radical‐induced apoptosis in human tumor cells is associated with telomere shortening but not telomerase inhibition and caspase activation

FEBS Letters

Ren, Jian-Guo¹  Xia, Hui-Li¹  Dai, Yao-Ren¹  Just, Tom² 

[1] Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, PR China;Department of Probe Applications, DAKO A/S, Produktionsvej 42, DK-2600 Glostrup, Denmark

关键词: Telomere;    Telomerase;    Hydroxyl radical;    Caspase;    Reactive oxygen species;    Mitochondrial transmembrane potential;    TUNEL;    terminal deoxynucleotidyltransferase (TdT)-mediated dUTP nick end labeling;    DAPI;    4′;    6-diamidino-2-phenylindole;    ROS;    reactive oxygen species;    GSH;    glutathione;    ΔΨ m;    mitochondrial transmembrane potential;    Ac-DEVD-CHO;    Ac-Asp-Glu-Val-Asp-acid aldehyde;    DODCB;    3;    3′-diethyloxadicarbocyanine;    DiOC6(3);    3;    3′-dihexyloxacarbocyanine iodide;    Rh 123;    rhodamine 123;    OH;    hydroxyl radical;    MPT pore;    mitochondrial permeability transition pore;   

DOI  :  10.1016/S0014-5793(00)02377-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 and telomerase/telomere. To address the interrelations between OH and telomerase/telomere in tumor cell killing, HeLa, 293 and MW451 cells were induced to undergo apoptosis with OH 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-induced apoptosis, telomere shortening took place while no changes in telomerase activity were observed. Our results suggest that OH-induced telomere shortening is not through telomerase inhibition but possibly a direct effect of OH on telomeres themselves indicating that telomere shortening but not telomerase inhibition is the primary event during OH-induced apoptosis. Strikingly, we also found that OH-induced apoptosis in HeLa cells is caspase-3-independent but is associated with reduction of mitochondrial transmembrane potential. Our results indicate that OH triggers apoptotic tumor cell death through a telomere-related, caspase-independent pathway.

【 授权许可】

Unknown