Cadmium (Cd2+) disrupts intercellular junctions and actin filaments in LLC-PK1 cells

Studies reported in the literature suggest that cadmium (Cd2+) may disrupt the junctions between cells in some tissues and cell culture systems. In order to examine this possibility in more detail, we have studied the effects of Cd2+ on the integrity of intercellular junctions in the established porcine renal epithelial cell line, LLC-PK1. Junctional integrity was assessed by monitoring the collapse of domes and by measuring changes in the transepithelial electrical resistance in confluent cell monolayers. Exposure to Cd2+ caused a rapid decrease in transepithelial resistance and the concomitant collapse of domes. These effects occurred at Cd2+ concentrations (20-60 microM) and durations of exposure (as little as 1 hr) that did not alter levels of ATP or kill the cells. Electron microscopic studies showed that Cd2+ caused time-dependent changes in adhering and occluding junctional complexes, which eventually resulted in the complete separation of the cells. Additional studies, in which rhodamine-coupled phalloidin was used to visualize F-actin, showed that Cd2+ altered the structure of actin filaments in the cells; there was a significant reduction in the amount of junction-associated F-actin and in the number of stress fibers. These results indicate that Cd2+ has relatively specific damaging effects on the adhering and occluding junctions between LLC-PK1 cells and that these effects may involve the disruption of cytoskeletal actin filaments.