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Lipid Peroxidation-Mediated Telomere Shortening in Hydroxyl Radical-Induced Apoptosis in HeLa Cells

Lipid Peroxidation-Mediated Telomere Shortening in Hydroxyl Radical-Induced Apoptosis in HeLa Cells
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摘要 Many anti cancer drugs have been found to trigger apoptosis in tumor cells through the production of reactive oxygen species (ROS) including hydroxyl radicals (·OH) regardless of chemical types. 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. The focus of this investigation was to examine the possible pathway of the apoptosis induced by ·OH production via Fe 2+ and H 2O 2. Results of the present study demonstrated that after exposure of HeLa cells to Fe 2+ H 2O 2 system, an increase in lipid peroxidation and reduction of GSH was observed. These events proceeded and triggered apoptosis, resulting in DNA fragmentation. More interestingly, we did not observe any changes of telomerase activity. However, the telomere length in apoptotic cells shortened significantly. We also found that GSH rescued ·OH induced HeLa cell death and prevened telomere shortening, and that 3,3' diethyoxadicarbocyanine (DODCB), a telomerase inhibitor, increased susceptibility of HeLa cells to ·OH induced apoptosis. Our results suggest that ·OH induced telomere shortening is not through telomerase inhibition but possibly a direct effect of ·OH on telomeres themselves via lipid peroxidation. Many anti cancer drugs have been found to trigger apoptosis in tumor cells through the production of reactive oxygen species (ROS) including hydroxyl radicals (·OH) regardless of chemical types. 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. The focus of this investigation was to examine the possible pathway of the apoptosis induced by ·OH production via Fe 2+ and H 2O 2. Results of the present study demonstrated that after exposure of HeLa cells to Fe 2+ H 2O 2 system, an increase in lipid peroxidation and reduction of GSH was observed. These events proceeded and triggered apoptosis, resulting in DNA fragmentation. More interestingly, we did not observe any changes of telomerase activity. However, the telomere length in apoptotic cells shortened significantly. We also found that GSH rescued ·OH induced HeLa cell death and prevened telomere shortening, and that 3,3' diethyoxadicarbocyanine (DODCB), a telomerase inhibitor, increased susceptibility of HeLa cells to ·OH induced apoptosis. Our results suggest that ·OH induced telomere shortening is not through telomerase inhibition but possibly a direct effect of ·OH on telomeres themselves via lipid peroxidation.
出处 《Tsinghua Science and Technology》 SCIE EI CAS 2001年第5期438-445,共8页 清华大学学报(自然科学版(英文版)
关键词 TELOMERE TELOMERASE hydoxyl radicals reactive oxygen species (ROS) lipid peroxidation malondialdehyde (MDA) telomere telomerase hydoxyl radicals reactive oxygen species (ROS) lipid peroxidation malondialdehyde (MDA)
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参考文献22

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