Low dose ionizing radiation-induced activation of connexin 43 expression

Area of Science:

• Molecular Biology
• Cell Biology
• Radiation Biology

Background:

• Connexin 43 (CX43) facilitates cell-to-cell communication.
• CX43's role in cellular response to ionizing radiation is known.
• The precise mechanisms of CX43 regulation by radiation require elucidation.

Purpose of the Study:

• To investigate how ionizing radiation affects connexin 43 expression.
• To identify the molecular mechanisms underlying radiation-induced CX43 regulation.

Main Methods:

• Cloning the human connexin 43 promoter into a Luciferase reporter plasmid.
• Measuring promoter activation in response to ionizing radiation in human fibroblasts and HeLa cells.
• Utilizing deletion and point mutations to define radiation-inducible regions.
• Confirming results with Northern and Western blotting.

Main Results:

• Ionizing radiation dose- and time-dependently activated the human connexin 43 promoter.
• Maximal induction (4.2-fold) occurred at 6 hours with 0.5 Gy; higher doses showed less induction.
• Promoter activation correlated with increased connexin 43 mRNA and protein levels.
• Low-dose radiation response depended on NFAT and AP1 binding sites (-2537 to -2110 bp).

Conclusions:

• Low doses of ionizing radiation transcriptionally upregulate connexin 43 expression.
• This upregulation is mediated through NFAT and AP1 binding sites on the promoter.