Abstract:
Intercellular communication through gap junctions (GJIC) is important in the control of cellular growth and differentiation and in many cellular processes including electrical synapsing, maintenance of homeostasis, hormonal response, and enbryonic development. The loss of intercellular communication may have numerous pathological consequences including teratogenesis and carcinogenesis. While a variety of agents have been shown to be capable of impairing GJIC, the mechanisms by which these agents act are poorly understood. Several previously published studies implied that glutathione (GSH) might be involved in the control og GJIC. Initial characterization of Rat-1 fibroblast variants with altered level of GSH suggested that there was an association with GJIC. Using these GSH variants, the relationship between gap junction intercellular communication and cellular glutathione level was further determined. There was a close correlation between the degree of GJIC and the cellular level of GSH among the seventeen cell variants tested here. The correlation between GJIC as measured by Fluorescence recovery after photobleaching (FRAP) and cellular GSH level when measured by monochlorobiman (MCB) / flow cytometry was essentially linear, (r=0.84). Cellular GSH content was also confirmed by a modified Tietze assay. Although the correlation between the GJIC and cellular GSH does not directly implicate that GSH controls GJIC, the data was consistent with an association of GJIC with GSH content in these Rat-1 fibroblast variants. This suggests that genetic or epigenetic changes within the cell which result in altered GSH homeostasis may predispose the cell to aberrant growth and differentiation via alterations in GJIC.