title: Iron Overload Causes Alterations of E-Cadherin in the Liver.
abstract: Iron overload causes tissue damage in the liver, but its initial effects at the molecular and cellular level are not well understood. Epithelial cadherin (E-cad) is a major adhesion protein in adherens junctions and is associated with several signal transduction pathways. Dysfunction of E-cad causes instability of adherens junctions, which leads to cell invasion, cell migration, and carcinogenesis. We found in liver samples from iron-overloaded mice that the apparent molecular mass of E-cad was reduced from 125 to 115 kDa in sodium dodecyl sulphate polyacrylamide gel electrophoresis under reducing conditions and immunoblotting, and that the cellular expression of E-cad was decreased in immunohistochemistry. The mRNA level of E-cad, however, did not change significantly, suggesting that the alterations are posttranslational. Interestingly, incubation of control liver extracts with Fe2+ alone also produced the same mobility shift. Neither an oxidant nor an antioxidant influenced this shift in vitro, suggesting that reactive oxygen species, which are generated by iron and known to cause damage to macromolecules, are not involved. Treatment of the 115 kDa E-cad with deferoxamine, an iron chelator, thus removing Fe2+, shifted the molecular mass back to 125 kDa, demonstrating that the shift is reversible. The observation also implies that the alteration that causes the mobility shift is not due to transcriptional control, deglycosylation, and proteolysis. This reversible mobility shift of E-cad has not been previously known. The alteration of E-cad that causes the mobility shift might be an initial step to liver diseases by iron overload.
authors: Institute of Pathophysiology, First Faculty of Medicine, Charles University in Prague, Czech Republic.
authors: Y
authors: Y
authors: Fujikura
authors: Institute of Pathophysiology, First Faculty of Medicine, Charles University in Prague, Czech Republic.
authors: J
authors: J
authors: Krijt
authors: Institute of Pathology, First Faculty of Medicine, Charles University in Prague, Czech Republic.
authors: C
authors: C
authors: Povýšil
authors: Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University in Prague, Czech Republic.
authors: Z
authors: Z
authors: Mělková
authors: Institute of Pathophysiology, First Faculty of Medicine, Charles University in Prague, Czech Republic.
authors: P
authors: P
authors: Přikryl
authors: Institute of Pathophysiology, First Faculty of Medicine, Charles University in Prague, Czech Republic.
authors: M
authors: M
authors: Vokurka
authors: Institute of Pathophysiology, First Faculty of Medicine, Charles University in Prague, Czech Republic.
authors: E
authors: E
authors: Nečas
mesh_terms: D000818:Animals; D015820:Cadherins / Q000737:chemistry*; D024202:Electrophoretic Mobility Shift Assay; D019190:Iron Overload / Q000503:physiopathology*; D008099:Liver / Q000737:chemistry / Q000503:physiopathology*; D051379:Mice; D011499:Protein Processing, Post-Translational
chemical_list: D015820:Cadherins