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 journalArticle

22 Scopus citations

Abstract

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
Volume81
Issue number969
DOIs
StatePublished - Sep 1 2008

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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