Expression of CONNEXIN43 is highly sensitive to ionizing radiation and other environmental stresses.

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  • Author(s): Azzam EI;Azzam EI; de Toledo SM; Little JB
  • Source:
    Cancer research [Cancer Res] 2003 Nov 01; Vol. 63 (21), pp. 7128-35.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print Cited Medium: Print ISSN: 0008-5472 (Print) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE
    • Publication Information:
      Publication: Baltimore, Md. : American Association for Cancer Research
      Original Publication: Chicago [etc.]
    • Subject Terms:
      Connexin 43/*biosynthesis ; Gene Expression Regulation/*radiation effects; Alpha Particles ; Animals ; Blotting, Western ; Cell Communication/physiology ; Cell Communication/radiation effects ; Cells, Cultured ; Connexin 43/genetics ; Connexin 43/metabolism ; Fibroblasts/metabolism ; Fibroblasts/physiology ; Fibroblasts/radiation effects ; Gamma Rays ; Gap Junctions/physiology ; Gap Junctions/radiation effects ; Gene Expression Profiling ; Hexachlorocyclohexane/pharmacology ; Hydrogen Peroxide/pharmacology ; Hyperthermia, Induced ; Mice ; Oligonucleotide Array Sequence Analysis ; Protein Processing, Post-Translational/radiation effects ; Rats ; Ultraviolet Rays ; Up-Regulation/radiation effects
    • Abstract:
      To gain a greater understanding of the mechanisms underlying the cellular responses to low-dose ionizing radiation, gene expression profiles were examined by microarray analysis of cDNA from confluent human diploid fibroblast cultures exposed to very low fluences of alpha-particles. The data, supported by Northern and Western analyses, indicate that radiation induces a significant up-regulation of CONNEXIN43 expression. This phenomenon was observed in a variety of irradiated cell types. These findings are consistent with our previous observations that connexin43 (cx43)-mediated gap-junction intercellular communication is involved in the bystander response observed in cell cultures exposed to fluences of alpha-particles by which only a very small fraction of the cell nuclei is traversed by a particle track (E. I. Azzam et al., Proc. Natl. Acad. Sci. USA, 98: 473-478, 2001). Increased mRNA levels in cells from irradiated cultures correlated with increased cx43 protein levels by approximately 4 h after irradiation. The induction of cx43 was observed by mean alpha-particle doses as low as 0.16 cGy, and also in cells exposed to gamma-rays, t-butyl hydroperoxide, and hyperthermia. Exposure to these stresses also resulted in post-translational modification of cx43; increased phosphorylation and hyperphosphorylation of the protein was observed. Up-regulation of cx43 expression in ionizing radiation exposed cells correlated with functional communication through gap junctions, as evidenced by dye transfer from irradiated to nonirradiated cells. In contrast, the response after UV radiation varied and was cell type-dependent. Overall, these data suggest a critical role for genes involved in intercellular communication in mediating the cellular responses to a variety of stresses.
    • Grant Information:
      1R01 CA 92262-01A1 United States CA NCI NIH HHS
    • Accession Number:
      0 (Connexin 43)
      59NEE7PCAB (Hexachlorocyclohexane)
      BBX060AN9V (Hydrogen Peroxide)
    • Publication Date:
      Date Created: 20031113 Date Completed: 20040116 Latest Revision: 20181130
    • Publication Date:
      20221213
    • Accession Number:
      14612506