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ToxSci Advance Access originally published online on November 9, 2005
Toxicological Sciences 2006 89(2):465-474; doi:10.1093/toxsci/kfj035
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Involvement of Gelsolin in Cadmium-Induced Disruption of the Mesangial Cell Cytoskeleton

Margarita D. Apostolova, Tania Christova and Douglas M. Templeton1

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M5S 1A8, Canada

Received September 19, 2005; accepted October 27, 2005

Cadmium (Cd2+) is known to cause a selective disruption of the filamentous actin cytoskeleton in the smooth muscle-like renal mesangial cell. We examined the effect of Cd2+ on the distribution of the actin-severing protein, gelsolin. Over 8 h, CdCl2 (10 µM) caused a progressive shift of gelsolin from a diffuse perinuclear and cytoplasmic distribution to a pattern decorating F-actin filaments. Over this time filaments were decreased in number in many cells, and membrane ruffling was initiated. Western blotting and 125I-F-actin gel overlays demonstrated an increase in actin-binding gelsolin activity in the cytoskeletal fraction of cell extracts following Cd2+ treatment. In in vitro polymerization assays, gelsolin acted as a nucleating factor and increased the rate of polymerization. Cytosolic extracts also increased the polymerization rate. Addition of Cd2+ together with gelsolin further increased the rate of polymerization. Gelsolin enhanced depolymerization of purified actin, and Cd2+ partially suppressed this effect. However, cytoskeletal extracts from Cd2+-treated cells also markedly increased depolymerization, suggesting further that Cd2+ may activate cellular component(s) such as gelsolin for actin binding. We conclude that a major effect of Cd2+ on the mesangial cell cytoskeleton is manifest through activating the association of gelsolin with actin, with gelsolin's severing properties predominating under conditions found in Cd2+-treated cells.

Key Words: F-actin; actin depolymerization; cadmium toxicity.


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