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Low dose ionizing radiation-induced activation of connexin 43 expression

Citation

Glover, D and Little, JB and Lavin, MF and Gueven, N, Low dose ionizing radiation-induced activation of connexin 43 expression, International Journal of Radiation Biology, 79, (12) pp. 955-964. ISSN 0955-3002 (2003) [Refereed Article]

Copyright Statement

Copyright 2003 Taylor & Francis Ltd

DOI: doi:10.1080/09553000310001632895

Abstract

Purpose: Connexin 43 has been implicated in the cellular response to ionizing radiation by enabling cell-to-cell communication. It is established here that the expression of connexin 43 is affected by ionizing radiation and the mechanism involved is investigated. Materials and methods: The human connexin 43 promoter was cloned into a Luciferase reporter plasmid and activation by ionizing radiation was measured in normal human fibroblasts as well as HeLa cells. The regions responsible for the radiation inducibility were defined using deletion and point mutations of the construct. The results were confirmed by Northern and Western blotting. Results: Ionizing radiation activates the human connexin 43 promoter in a time- and dose-dependent manner with a maximal induction (4.2-fold 0.58) after 6 h and a dose of 0.5 Gy. Higher doses up to 5 Gy led to a less marked increase (2-fold) over the same period. This promoter activation was associated with comparable increases in both connexin 43 mRNA and protein levels. The low dose radiation response of the promoter is mainly dependent on consensus binding sites for nuclear factor of activated T-cells (NFAT) and activator protein (AP1) in a region -2537 and -2110 bp from the transcriptional start site as determined by mutation analysis. Conclusions: Low doses of ionizing radiation induce the transcriptional upregulation of connexin 43 expression employing NFAT and AP1 sites.

Item Details

Item Type:Refereed Article
Keywords:Connexin 43, promoter, ionizing radiation
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Signal Transduction
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
Author:Gueven, N (Dr Nuri Guven)
ID Code:79321
Year Published:2003
Web of Science® Times Cited:20
Deposited By:Pharmacy
Deposited On:2012-08-31
Last Modified:2016-10-19
Downloads:0

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