Enhanced Connexin 43 Expression Delays Intra-Mitoitc Duration and Cell Cycle Traverse Independently of Gap Junction Channel Function

Johnstone, Scott R., Best, A. K., Wright, C. S., Isakson, B. E., Errington, Rachel Jane ORCID: https://orcid.org/0000-0002-8016-4376 and Martin, P. E. 2010. Enhanced Connexin 43 Expression Delays Intra-Mitoitc Duration and Cell Cycle Traverse Independently of Gap Junction Channel Function. Journal of Cellular Biochemistry 110 (3) , pp. 772-782. 10.1002/jcb.22590

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Abstract

Connexins (Cx) and gap junction (GJ) mediated communication has 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, 18α-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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General)
Uncontrolled Keywords:	connexin 43; gap junction; cell cycle traverse; cell migration; mitotic duration
Publisher:	Wiley
ISSN:	1097-4644
Last Modified:	21 Oct 2022 09:37
URI:	https://orca.cardiff.ac.uk/id/eprint/37113

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