Cadmium is more toxic to LLC-PK1 cells than to MDCK cells acting on the cadherin-catenin complex.
Cadmium toxicity to renal cells was investigated in Madin-Darby canine kidney (MDCK) and LLC-PK1 cells as models of the distal tubule/collecting duct and proximal tubule, respectively. Cells were grown on two-compartment filters and exposed to 0.1-50 microM Cd2+. In MDCK cells, Cd2+ was more toxic from the basolateral than from the apical side and dependent on the extracellular Ca2+ concentration. Toxicity was evident within 24 h, as shown by a decrease in transepithelial resistance (TER), reduced proliferation (bromodeoxyuridine incorporation), reduction in ATP concentration, and morphological changes. On confocal microscopy, E-cadherin and alpha-catenin staining patterns indicated interference with the cadherin-catenin complex. LLC-PK1 cells showed a similar toxicity pattern, which was evident at lower Cd2+ concentrations. An increase of E-cadherin and alpha-catenin molecules in the Triton X-100-insoluble fraction was detectable at high Cd2+ concentrations in LLC-PK1 cells but not in MDCK cells. Lactate dehydrogenase release indicated membrane leakage in LLC-PK1 cells. Rhodamine-phalloidin staining, a probe for F-actin filaments, demonstrated alterations of the actin cytoskeleton in both cell lines. In conclusion, cadmium caused ATP depletion and interfered with the cadherin-catenin complex and probably the tight junctions changing renal cell morphology and function.
Department of Pediatrics, Albert-Ludwigs-University, D-79106 Freiburg, Germany.
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Zimmerhackl
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Wiegele
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Brandis
D000818:Animals; D015820:Cadherins / Q000187:drug effects / Q000502:physiology*; D002104:Cadmium / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007668:Kidney; D007685:Kidney Tubules, Collecting; D007687:Kidney Tubules, Proximal; D018374:LLC-PK1 Cells; D008564:Membrane Potentials / Q000187:drug effects; D013552:Swine
D015820:Cadherins; D003598:Cytoskeletal Proteins; D002104:Cadmium