Expression of telomerase inhibits hydroxyl radical-induced apoptosis in normal telomerase negative human lung fibroblasts

• Published in: FEBS letters Vol. 488; no. 3; pp. 133 - 138
• Main Authors: Ren, Jian-Guo, Xia, Hui-Li, Tian, Yan-Mei, Just, Tom, Cai, Guo-Ping, Dai, Yao-Ren
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 19-01-2001
• Subjects: Apoptosis; Apoptosis - drug effects; Caspase 3; Caspases - metabolism; Clone Cells - enzymology; Clone Cells - metabolism; DAPI, 4′,6-diamidino-2-phenylindole; Dose-Response Relationship, Drug; Fibroblasts - drug effects; Fibroblasts - enzymology; Fibroblasts - metabolism; Gene Deletion; hLF, human lung fibroblast; hTERT, human telomerase reverse transcriptase; Human telomerase reverse transcriptase subunit; Humans; Hydroxyl radical; Hydroxyl Radical - antagonists & inhibitors; Hydroxyl Radical - pharmacology; Lung; OH, hydroxyl radical; PI, propidium iodide; Telomerase; Telomerase - genetics; Telomerase - metabolism; Telomere; Telomere - chemistry; Telomere - genetics; Telomere - metabolism; Transfection; TRAP, telomeric repeat amplification protocol; TUNEL, terminal deoxynucleotidyltransferase (TdT)-mediated dUTP-digoxigenin nick end labeling; OH, hydroxyl radical; Human telomerase reverse transcriptase subunit; PI, propidium iodide; hLF, human lung fibroblast; hTERT, human telomerase reverse transcriptase; TRAP, telomeric repeat amplification protocol; DAPI, 4′,6-diamidino-2-phenylindole; Telomerase; Telomere; Hydroxyl radical; Apoptosis; TUNEL, terminal deoxynucleotidyltransferase (TdT)-mediated dUTP-digoxigenin nick end labeling
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(00)02397-8

In tumor cells telomerase activity is associated with resistance to apoptosis and the introduction of the human telomerase reverse transcriptase (hTERT) subunit into normal human cells is associated with life span extension of the cells. To determine the role of telomerase in regulating apoptosis, telomerase negative human embryo lung fibroblasts were transfected with the hTERT gene. Unlike the control fibroblasts, the telomerase-expressing cells had elongated telomeres and were resistant to apoptosis induced by hydroxyl radicals. The results indicate that expression of telomerase and, thus, the maintenance of telomere length in normal human somatic cells caused resistance to not only cellular senescence but also apoptosis. Moreover, we found that hydroxyl radical-induced apoptosis in telomerase-expressing and control fibroblasts was caspase-3 independent. These findings have revealed a new type of interrelation between telomerase and caspase-3, which may indicate that in this case the expressed telomerase may inhibit apoptosis at a site not related to the caspase-3 cascade.