Induced telomerase activity in primary aortic endothelial cells by low-LET γ-radiation is mediated through NF-κB activation

Mohan Natarajan, S. Mohan, R. Konopinski, R. A. Otto, T. S. Herman

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Our objective was to understand the mechanism through which cells that initially survive irradiation could acquire survival advantage. In this study, we show evidence that low-linear energy transfer c-radiation can induce telomerase enzyme activity in primary aortic endothelial cells, and that an upstream regulator, nuclear factor kappa B (NF-κB), controls this activation. Telomeric repeat amplification protocol (TRAP) assay showed that cells exposed to a dose of 2 Gy induce telomerase activity. Subsequent analysis revealed that radiation-induced telomeric activity is regulated at the transcriptional level by triggering activation of the promoter of the telomerase catalytic subunit, telomerase reverse transcriptase (TERT). A mechanistic study revealed that NF-κB becomes functionally activated upon radiation exposure and mediates the upregulation of telomerase activity by binding to the κB-binding region in the promoter region of the TERT gene. More significantly, elimination of the NF-κB recognition site on the telomerase promoter or inhibition of NF-κB by ectopically expressing the inhibitor protein IκBα mutant (IκBαS32A/S36A)) compromises radiation-induced telomerase promoter activation. Consistent with the notion that NF-κB mediates γ-ray-induced telomerase responses, TRAP assay revealed that ectopically expressed IκBα S32A/S36A) also attenuated telomerase enzyme activity. These findings indicate that NF-κB activation following ionizing radiation exposure may elicit a survival advantage by upregulating and maintaining telomerase activity.

Original languageEnglish (US)
Pages (from-to)711-720
Number of pages10
JournalBritish Journal of Radiology
Issue number969
StatePublished - Sep 2008

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


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