Low dose ionizing radiation-induced activation of connexin 43 expression

Glover, D., Little, J.B., Lavin, M.F. and Gueven, N. (2003) Low dose ionizing radiation-induced activation of connexin 43 expression. International Journal of Radiation Biology, 79 12: 955-964. doi:10.1080/09553000310001632895


Author Glover, D.
Little, J.B.
Lavin, M.F.
Gueven, N.
Title Low dose ionizing radiation-induced activation of connexin 43 expression
Journal name International Journal of Radiation Biology   Check publisher's open access policy
ISSN 0955-3002
Publication date 2003-12-01
Sub-type Article (original research)
DOI 10.1080/09553000310001632895
Volume 79
Issue 12
Start page 955
End page 964
Total pages 10
Editor R.P. Hill
A.M. Rauth
Place of publication Abingdon, U.K.
Publisher Taylor & Francis
Collection year 2003
Language eng
Subject C1
320304 Medical Biochemistry - Nucleic Acids
730108 Cancer and related disorders
Formatted 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 6h and a dose of 0.5 Gy. Higher doses up to 5Gy 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 22110 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.
Keyword Biology
Nuclear Science & Technology
Radiology, Nuclear Medicine & Medical Imaging
Nf-kappa-b
Intercellular Communication
Alpha-particles
Oxidative Stress
Gene-expression
Binding-sites
Gap-junctions
Rat-liver
Cells
Ap-1
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2004 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 11:25:13 EST