Induced telomerase activity in primary aortic endothelial cells by low-LET gamma-radiation is mediated through NF-kappaB activation.
BRITISH JOURNAL OF RADIOLOGY(2014)
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 gamma-radiation can induce telomerase enzyme activity in primary aortic endothelial cells, and that an upstream regulator, nuclear factor kappa B (NF-kappa B), 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-kappa B becomes functionally activated upon radiation exposure and mediates the upregulation of telomerase activity by binding to the kappa B-binding region in the promoter region of the TERT gene. More significantly, elimination of the NF-kappa B recognition site on the telomerase promoter or inhibition of NF-kappa B by ectopically expressing the inhibitor protein I kappa B alpha mutant (I kappa B alpha(S32A/536A))) compromises radiation-induced telomerase promoter activation. Consistent with the notion that NF-kappa B mediates gamma-ray-induced telomerase responses, TRAP assay revealed that ectopically expressed I kappa B alpha(S32A/S36A)) also attenuated telomerase enzyme activity. These findings indicate that NF-kappa B activation following ionizing radiation exposure may elicit a survival advantage by upregulating and maintaining telomerase activity. (c) The British Institute of Radiology.
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Key words
endothelial cell,ionizing radiation,reverse transcriptase,linear energy transfer,enzyme activity
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