Journal of Cellular Biochemistry

Enhanced connexin 43 expression delays intra-mitoitc duration and cell cycle traverse independently of gap junction channel function

Authors

  • Scott R. Johnstone,

    1. Department of Biological and Biomedical Sciences, School of Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Rd, Glasgow, Scotland G4 0BA, UK
    2. Robert M. Berne Cardiovascular Research Centre, University of Virginia School of Medicine, PO Box 801394, Charlottesville, Virginia 29908
    3. School of Medicine, Cardiff University, Cardiff, Wales CF14 4XN, UK
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  • Angela K. Best,

    1. Robert M. Berne Cardiovascular Research Centre, University of Virginia School of Medicine, PO Box 801394, Charlottesville, Virginia 29908
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  • Catherine S. Wright,

    1. Department of Biological and Biomedical Sciences, School of Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Rd, Glasgow, Scotland G4 0BA, UK
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  • Brant E. Isakson,

    1. Robert M. Berne Cardiovascular Research Centre, University of Virginia School of Medicine, PO Box 801394, Charlottesville, Virginia 29908
    2. Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia
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  • Rachel J. Errington,

    1. School of Medicine, Cardiff University, Cardiff, Wales CF14 4XN, UK
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  • Patricia E. Martin

    Corresponding author
    1. Department of Biological and Biomedical Sciences, School of Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Rd, Glasgow, Scotland G4 0BA, UK
    • Department of Biological and Biomedical Sciences, School of Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Rd, Glasgow, Scotland G4 0BA, UK.
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  • The authors have no conflict of interest to declare.

Abstract

Connexins (Cxs) and gap junction (GJ)-mediated communication have been linked with the regulation of cell cycle traverse. However, it is not clear whether Cx expression or GJ channel function are the key mediators in this process or at what stage this regulation may occur. We therefore tested the hypothesis that enhanced Cx expression could alter the rate of cell cycle traverse independently of GJ channel function. Sodium butyrate (NaBu) or anti-arrhythmic peptide (AAP10) were used to enhance Cx expression in HeLa cells stably expressing Cx43 (HeLa-43) and primary cultures of human fibroblasts (HFF) that predominantly express Cx43. To reduce GJ-mediated communication, 18-α-glycyrrhetinic acid (GA) was used. In HeLa-43 and HFF cells, NaBu and AAP10 enhanced Cx43 expression and increased channel function, while GA reduced GJ-mediated communication but did not significantly alter Cx43 expression levels. Timelapse microscopy and flow cytometry of HeLa-WT (wild-type, Cx deficient) and HeLa-43 cells dissected cell cycle traverse and enabled measurements of intra-mitotic time and determined levels of G1 arrest. Enhanced Cx43 expression increased mitotic durations corresponding with a G1 delay in cell cycle, which was linked to an increase in expression of the cell cycle inhibitor p21waf1/cip1 in both HeLa-43 and HFF cells. Reductions in Cx43 channel function did not abrogate these responses, indicating that GJ channel function was not a critical factor in reducing cell proliferation in either cell type. We conclude that enhanced Cx43 expression and not GJ-mediated communication, is involved in regulating cell cycle traverse. J. Cell. Biochem. 110: 772–782, 2010. © 2010 Wiley-Liss, Inc.

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