Telomerase confers resistance to caspase-mediated apoptosis.

Yira Bermudez, Diana Erasso, Nicole C. Johnson, Michelle Y. Alfonso, Nancy E. Lowell, Patricia A. Kruk

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

There is growing evidence that accelerated telomeric attrition and/or aberrant telomerase activity contributes to pathogenesis in a number of diseases. Likewise, there is increasing interest to develop new therapies to restore or replace dysfunctional cells characterized by short telomeric length using telomerase-positive counterparts or stem cells. While telomerase adds telomeric repeats de novo contributing to enhanced proliferative capacity and lifespan, it may also increase cellular survival by conferring resistance to apoptosis. Consequently, we sought to determine the involvement of telomerase for reduced apoptosis using ovarian surface epithelial cells. We found that expression of hTERT, the catalytic component of telomerase, was sufficient and specific to reduce caspase-mediated cellular apoptosis. Further, hTERT expression reduced activation of caspases 3, 8, and 9, reduced expression of pro-apoptotic mitochondrial proteins t-BID, BAD, and BAX and increased expression of the anti-apoptotic mitochondrial protein, Bcl-2. The ability of telomerase to suppress caspase-mediated apoptosis was p-jnk dependent since abrogation of jnk expression with jip abolished resistance to apoptosis. Consequently, these findings indicate that telomerase may promote cellular survival in epithelial cells by suppressing jnk-dependent caspase-mediated apoptosis.

Original languageEnglish (US)
Pages (from-to)155-167
Number of pages13
JournalClinical interventions in aging
Volume1
Issue number2
DOIs
StatePublished - 2006

ASJC Scopus subject areas

  • Geriatrics and Gerontology

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