Modulation of telomerase activity and human telomerase reverse transcriptase expression by caspases and Bcl-2 family proteins in cisplatin-induced cell death = 시스플라틴 유도 세포사멸에서 caspases 및 Bcl-2 family 단백질에 의한 끝분절효소 활성 및 인간끝분

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Title
Modulation of telomerase activity and human telomerase reverse transcriptase expression by caspases and Bcl-2 family proteins in cisplatin-induced cell death = 시스플라틴 유도 세포사멸에서 caspases 및 Bcl-2 family 단백질에 의한 끝분절효소 활성 및 인간끝분
Author(s)
Yuk-Pheel Park; Seung-Chul Choi; Mi Young Cho; Eun Young Song; Jae Wha Kim; S G Paik; Y K Kim; J W Kim; Hee Gu Lee
Bibliographic Citation
Korean Journal of Laboratory Medicine, vol. 26, no. 4, pp. 287-293
Publication Year
2006
Abstract
BACKGROUND: Human telomerase is a ribonucleoprotein polymerase, which synthesizes telomeric repeat sequences, and human telomerase reverse transcriptase (hTERT) has been identified as the catalytic subunit, as well as the rate-limiting component, of telomerase. In this study, we attempted to identify the modulators of telomerase, and to determine the molecular mechanisms underlying cisplatin-induced apoptosis. METHODS: To determine the role of telomerase in cisplatin-induced apoptosis, we measured telomerase activity and analyzed apoptosis using PI and trypan blue staining. Also, we inhibited the caspase activations using Z-VAD-fmk to analyze the effects on expression of hTERT protein. Finally, we induced the transient co-expression of the Bcl-2 and Bak genes in HEK293 cells, and then, the telomerase activity and expression of hTERT were evaluated. RESULTS: In the Bcl-2-overexpressing HeLa cells, telomerase activity was more enhanced, and cell death was reduced to 40-50% that of the mock controls. This finding suggests that Bcl-2-induced telomerase activity exerts an antiapoptotic effect in cisplatin-induced death. As caspase activation was inhibited via Z-VAD-fmk, the hTERT protein was recovered in the mock controls, but not in the Bcl-2-overexpressing cells. This suggests that the expression of hTERT can be regulated by caspases, but Bcl-2 was located within the upstream pathway. Moreover, when the Bcl-2 and Bak genes were co-transfected into the HEK293, both telomerase activity and hTERT protein were prominently reduced. CONCLUSIONS: Bcl-2-induced telomerase activity inhibits cisplatin-induced apoptosis in HeLa cells, and can be regulated via both caspases and the interaction of Bcl-2 and Bak.
Keyword
ApoptosisCisplatinhTERTBcl-2Bak
ISSN
I000-0170
Publisher
South Korea
DOI
http://dx.doi.org/10.3343/kjlm.2006.26.4.287
Type
Article
Appears in Collections:
Division of Biomaterials Research > Cell Factory Research Center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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