Cadmium is more toxic to llc-pk1 cells than to mdck cells acting on
the cadherin-catenin-complex.
Zimmerhackl, L. B., F. Momm, G. Wiegele, and M. Brandis.
Department of Pediatrics, Albert-Ludwigs-University, Freiburg,
Germany
APStracts 5:0078F, 1998.
Cadmium toxicity to renal cells was investigated in MDCK- and LLC-PK1
-cells, as models of the distal tubule/collecting duct and proximal
tubule, respectively. Cells were grown on two com partment filters
and exposed to 0.1-50 [mu]mol Cd2+. In MDCK-cells Cd2+ was more toxic
from the basolateral than from the apical side and dependent on the
extracellular Ca2+-concentration. Tox icity was evident within 24hrs,
as shown by a decrease in transepithelial resistance (TER), re duced
proliferation (BrdU-incorporation), reduction in ATP concentration
and morphological changes. On confocal microscopy E-cadherin and
[alpha]-catenin staining pattern indicated interfer ence 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. LDH release indicated membrane
leakage in LLC-PK1-cells. Rhodamine-phalloidin staining, a probe for
-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 morphol ogy and function.
Received 19 November 1996; accepted in final form 19 March 1998.
APS Manuscript Number F322-6.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 24 April 1998