title: Disruption of cadherin/catenin expression, localization, and interactions during HgCl2-induced nephrotoxicity.
abstract: 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, colocalization studies, and coimmunoprecipitation, we conclude that two distinct cadherin/catenin complexes exist in adult mouse kidney proximal tubules: N-cadherin/beta-catenin/alpha-catenin and E-cadherin/beta-catenin/alpha-catenin/p120-catenin. In the distal tubule, E-cadherin/beta-catenin/alpha-catenin and E-cadherin/gamma-catenin/alpha-catenin complexes are present. Male C3H mice were challenged with 0-25 micromol/kg mercuric chloride i.p. (6-48 h) to assess the impact of nephrotoxicity on cadherin/catenin complexes. Plasma creatinine and blood urea nitrogen were increased between 6 and 48 h, indicating the onset of renal failure. In addition, histological evaluation demonstrated alterations in the proximal tubules. At 24 h, we observed decreases in Ksp- and N-cadherin, but not in E-cadherin. Additionally, alpha-catenin expression was decreased, in the absence of changes in beta-, gamma-, and p120-catenin. The early stages (6 h) of mercuric chloride-induced nephrotoxicity were associated with disruption of complex integrity. N-cadherin and alpha-catenin localizations were disrupted at 6 h. These changes in cadherin and catenin localization corresponded with a decrease in the coimmunoprecipitation of alpha-catenin with both beta-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.
authors.affiliation: Department of Medical Pharmacology and Toxicology, College of Medicine, Texas A&M University System Health Science Center, College Station 77843-1114, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.forename: Dana
authors.initials: D
authors.lastname: Dean
authors.forename: Robert C
authors.initials: RC
authors.lastname: Burghardt
authors.forename: Alan R
authors.initials: AR
authors.lastname: Parrish
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D003404:Creatinine / Q000097:blood; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D051180:Desmoplakins; D005455:Fluorescent Antibody Technique; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity; D051379:Mice; D008809:Mice, Inbred C3H; D010750:Phosphoproteins / Q000096:biosynthesis*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis*; D051178:alpha Catenin; D051176:beta Catenin; D000095002:Delta Catenin
chemical_list: C495267:CTNNB1 protein, mouse; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D010750:Phosphoproteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; C502406:fat1 protein, mouse; D008627:Mercuric Chloride; D003404:Creatinine; D000254:Sodium-Potassium-Exchanging ATPase; D000095002:Delta Catenin; C000722349:Ctnnd1 protein, mouse