title: Cadmium (Cd2+) disrupts E-cadherin-dependent cell-cell junctions in MDCK cells.
abstract: Previous studies from our laboratory have shown that Cd2+ can selectively disrupt E-cadherin-dependent cell-cell junctions in the porcine renal epithelial cell line, LLC-PK1. The objective of the present studies was to determine whether or not Cd2+ could produce similar effects in Madin-Darby canine kidney (MDCK) cells, an immortal epithelial cell line derived from dog kidney. This is an important issue because MDCK cells have been used extensively as a model system to study the basic mechanisms of E-cadherin-dependent cell-cell adhesion. MDCK cells on permeable membrane supports were exposed to Cd2+ by adding CdCl2 to either the apical or the basolateral compartment. The integrity of cell-cell junctions was assessed by morphologic observation of the cells and by monitoring the transepithelial electrical resistance. The results showed that exposure to 10-40 microM Cd2+ for 15 min-4 h caused the cells to separate from each other without detaching from the growing surface. The separation of the cells was accompanied by a marked drop in the transepithelial electrical resistance, a loss of E-cadherin from the cell-cell contacts, and a reorganization of the actin cytoskeleton. These effects were much more pronounced when Cd2+ was added basolaterally than when it was added apically. Moreover, the effects of Cd2+ were qualitatively similar to those observed when the cells were incubated in Ca(2+)-free medium. These results show that Cd2+ can disrupt E-cadherin-dependent cell-cell junctions in MDCK cells, and they indicate that this cell line would be an appropriate model for further mechanistic studies in this area.
authors.affiliation: Department of Pharmacology, Midwestern University, Downers Grove, Illinois 60515, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Prozialeck
authors.forename: P C
authors.initials: PC
authors.lastname: Lamar
mesh_terms: D000199:Actins / Q000648:ultrastructure; D000818:Animals; D015820:Cadherins / Q000494:pharmacology*; D002104:Cadmium / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D003599:Cytoskeleton / Q000648:ultrastructure; D004285:Dogs; D017097:Electric Impedance; D004848:Epithelium / Q000187:drug effects / Q000648:ultrastructure; D007365:Intercellular Junctions / Q000187:drug effects* / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000648:ultrastructure*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D002104:Cadmium; D007770:L-Lactate Dehydrogenase; D002118:Calcium