title: Modulation of telomerase activity and human telomerase reverse transcriptase expression by caspases and bcl-2 family proteins in Cisplatin-induced cell death.
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.
authors.affiliation: Cellomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea. hglee@kribb.re.kr.
authors.forename: Yuk Pheel
authors.initials: YP
authors.lastname: Park
authors.forename: Seung Chul
authors.initials: SC
authors.lastname: Choi
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Cho
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Song
authors.forename: Jae Wha
authors.initials: JW
authors.lastname: Kim
authors.forename: Sang Gi
authors.initials: SG
authors.lastname: Paik
authors.forename: Young Kwon
authors.initials: YK
authors.lastname: Kim
authors.forename: Jong Wan
authors.initials: JW
authors.lastname: Kim
authors.forename: Hee Gu
authors.initials: HG
authors.lastname: Lee