ToxSci Advance Access published online on April 14, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh143
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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1 Department of Medical Pharmacology & Toxicology, College of Medicine, Texas A&M University System Health Science Center
* To whom correspondence should be addressed. E-mail: parrish{at}medicine.tamu.edu.
The cadherin/catenin complex is an essential regulator of intercellular adhesion and is critical for the establishment of epithelial cell polarity. The purpose of this study was to 1) determine the spatial pattern of cadherin and catenin expression, colocalization and interaction along the mouse nephron and 2) investigate the expression, localization and interaction of proximal tubular cadherins and catenins during mercuric chloride-induced nephrotoxicity. Using a combination of Western blot analysis, co-localization studies and co-immunoprecipitation, we conclude that two distinct cadherin/catenin complexes exist in adult mouse kidney proximal tubules; N-cadherin/
© 2004 Toxicological Sciences © Society of Toxicology 2004; all rights reserved.
Systems Evaluation
Disruption of Cadherin/Catenin Expression, Localization and Interactions During HgCl2-Induced Nephrotoxicity
2 Department of Veterinary Anatomy and Public Health, College of Veterinary Medicine, Texas A&M University
Abstract 
-catenin/
-catenin and E-cadherin/-catenin/-catenin/p120-catenin. In the distal tubule, E-cadherin/-catenin/-catenin and E-cadherin/
-catenin/-catenin complexes are present. Male C3H mice were challenged with 0-25 µmol/kg mercuric chloride i.p (6-48 hr) to assess the impact of nephrotoxicity on cadherin/catenin complexes. Plasma creatinine and blood urea nitrogen were increased between 6-48 hr, indicating the onset of renal failure. In addition, histological evaluation demonstrated alterations in the proximal tubules. At 24 hr, decreases in Ksp- and N-cadherin, but not E-cadherin, were observed. Additionally, -catenin expression was decreased, in the absence of changes in -, -, and p120-catenin. The early stages (6 hr) of mercuric chloride-induced nephrotoxicity were associated with disruption of complex integrity. N-cadherin and -catenin localization was disrupted at 6 hr. These changes in cadherin and catenin localization corresponded with a decrease in the coimmunoprecipitation of -catenin with both -catenin and N-cadherin. Interestingly, these changes occurred at the same time that aberrant staining of Na+K+-ATPase staining was seen. Taken together, these data suggest that alterations in cadherin and catenin expression, localization and interaction are associated with nephrotoxicity.
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