Comparison of the cytotoxic effects of cadmium (Cd(2+)) in high and low resistance strains of MDCK cells that express different levels of E-Cadherin.
Previous studies from our laboratory have shown that cadmium (Cd(2+)) can disrupt the adhering and occluding junctions between MDCK cells. Recently, we have obtained evidence to suggest that Cd(2+) produces this effect by interacting with E-cadherin, a Ca(2+)-dependent cell adhesion molecule that is localized at the adhering junctions of epithelial cells. The objective of the present study was to examine the junctional and cytotoxic effects of Cd(2+) in subcloned strains of MDCK cells that express different levels of E-cadherin. One strain (MDCK I) expresses high levels of E-cadherin and develops a transepithelial electrical resistance of more than 800 Omega.cm(2), whereas the other strain (MDCK II) expresses much lower levels of E-cadherin and develops a transepithelial resistance of less than 100 Omega.cm(2). The results showed that exposure to 20 mum Cd(2+) for 2-4 hours caused a pronounced loss of E-cadherin from the cell borders in both strains of cells. In the MDCK I cells, the loss of E-cadherin coincided with a decrease in the transepithelial electrical resistance and the loss of the tight junction-associated proteins, ZO-1 and occludin, from the cell borders. By contrast, the MDCK II cells first exhibited a significant increase in the transepithelial electrical resistance that did not begin to decline until the cells had been exposed for 4-6 hours, a time that coincided with the loss of ZO-1 and occludin from the cell borders. Additional results showed that the MDCK I cells were slightly more sensitive to the lethal effects of Cd(2+) than were the MDCK II cells. These findings indicate that E-cadherin may be an early target for Cd(2+) toxicity in both high and low resistance strains of MDCK cells. However, they also suggest that the disruption of E-cadherin-dependent cell-cell junctions may trigger somewhat different responses in the two cell lines.
Prozialeck
W C
WC
Department of Pharmacology, Midwestern University, Downers Grove, IL 60515, USA.
Lamar
P C
PC