ATP7B copper-regulated traffic and association with the tight junctions: copper excretion into the bile.: ATP7B and copper excretion by liver
| Autor: | Hernandez, Sonia, Tsuchiya, Yo, García-Ruiz, Josefa, Lalioti, Vassiliki, Nielsen, Søren, Cassio, Doris, Sandoval, Ignacio |
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| Přispěvatelé: | Centro de Biología Molecular Severo Ochoa [Madrid] (CBMSO), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), The Water and Salt Research Center, Signalisation cellulaire et calcium, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by grants of the Ministerio de Educacion y Ciencia from the Spanish Government (BFU-2005-07903, GEN2003-20662-C07-06) to I.V.S., Ministerio de Educacion y Ciencia from the Spanish Government (BFU-2005-07903, U757, . |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
MESH: Humans
MESH: Cell Line Tumor MESH: Rats MESH: Microscopy Fluorescence MESH: Rats Wistar [SDV.BC]Life Sciences [q-bio]/Cellular Biology digestive system MESH: Male MESH: Hepatocytes MESH: Copper MESH: Liver Neoplasms Experimental MESH: Cation Transport Proteins MESH: Antibodies Neoplasm MESH: Liver Neoplasms MESH: Adenosine Triphosphatases MESH: Blotting Western MESH: Animals MESH: Carcinoma Hepatocellular [SDV.BC] Life Sciences [q-bio]/Cellular Biology MESH: Bile MESH: Liver MESH: Electrophoresis Polyacrylamide Gel |
| Zdroj: | Gastroenterology Gastroenterology, Elsevier, 2008, 134 (4), pp.1215-23. ⟨10.1053/j.gastro.2008.01.043⟩ |
| ISSN: | 0016-5085 1528-0012 |
| DOI: | 10.1053/j.gastro.2008.01.043⟩ |
| Popis: | International audience; BACKGROUND & AIMS: The copper transporter ATP7B plays a central role in the elimination of excess copper by the liver into the bile, yet the site of its action remains controversial. The studies reported here examine the correspondence between the site of ATP7B action and distribution and the pathways of copper disposal by the liver. METHODS: Microscopy and cell fractionation studies of polarized Can 10 cells forming long-branched bile canaliculi have been used to study the cellular distribution of ATP7B. Copper excretion into the bile was studied in perfused rat liver. RESULTS: Copper excess provokes a massive download of the ATP7B retained in the trans-Golgi network into the bile canalicular membrane. Furthermore, a stable ATP7B pool is localized to the tight junctions that seal the bile canaliculi. The profile of Cu(64) excretion into the bile by isolated rat livers perfused under one-pass conditions provides evidence of copper excretion by 2 separate mechanisms, transcytosis across the hepatocyte and paracellular transport throughout the tight junctions. CONCLUSIONS: Whereas the ATP7B retained in the trans-Golgi-network is massively translocated to the bile canalicular membrane in response to increased copper levels, a pool of ATP7B associated with the tight junctions remains stable. In situ studies indicate that copper is excreted into the bile by 2 separate pathways. The results are discussed in the frame of the normal and impeded excretion of copper into the bile. |
| Databáze: | OpenAIRE |
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