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Changes in the gap junctional intercellular communication in renal tubular epithelial cells in vitro treated with
M Noguchi1, K Nomata, J Watanabe
1Department of Urology, Nagasaki University School of Medicine, Japan.
Abstract:
Gap junctional intercellular communications (GJIC) are known as the channels for the direct transfer of cytoplasmic molecules between neighboring cells and are lost during transformation of normal cells. To study the function and the molecular mechanism for the loss of GJIC, the effects of dimethylnitrosamine, KBrO3 and FeSO4 x 7H2O, which are known as chemical tumor promoters of the kidney on the GJIC function and the expression of connexin 43 of Madin-Darby canine kidney (MDCK) epithelial cells, were examined. These tumor promoters inhibited the GJIC in MDCK cells. The expression of connexin 43 mRNA and connexin 43 protein was not altered by these treatments, whereas immunocytochemical study revealed that the distribution of connexin 43 protein was changed from the cell surface to the cytoplasma. These data suggest that blockage of GJIC in MDCK cells treated with renal carcinogens support the hypothesis that loss of GJIC might be important in renal carcinogenesis.
Insights
Chemical tumor promoters inhibit gap junctional intercellular communication (GJIC) in kidney cells. This loss of GJIC, crucial for cell communication, may play a role in kidney cancer development.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Gap junctional intercellular communication (GJIC) facilitates direct cell-to-cell transfer of molecules.
- Loss of GJIC is observed during cellular transformation and is implicated in carcinogenesis.
- Connexin 43 is a key protein forming gap junctions.
Purpose of the Study:
- To investigate the effects of chemical kidney tumor promoters on GJIC function and connexin 43 expression in Madin-Darby canine kidney (MDCK) cells.
- To elucidate the molecular mechanisms underlying the loss of GJIC induced by these promoters.
Main Methods:
- Treatment of MDCK cells with chemical carcinogens: dimethylnitrosamine, KBrO3, and FeSO4 x 7H2O.
- Assessment of GJIC function using established assays.
- Analysis of connexin 43 expression at both mRNA and protein levels.
- Immunocytochemical localization of connexin 43 protein.
Main Results:
- Chemical tumor promoters significantly inhibited GJIC in MDCK cells.
- Connexin 43 mRNA and protein expression levels remained unchanged.
- Immunocytochemistry revealed a shift in connexin 43 distribution from the cell surface to the cytoplasm.
Conclusions:
- The inhibition of GJIC by renal carcinogens in MDCK cells supports the hypothesis that GJIC loss is important in renal carcinogenesis.
- The data suggest that altered distribution, rather than expression levels, of connexin 43 contributes to GJIC blockage.
- These findings highlight the role of disrupted cell-cell communication in kidney cancer development.