Differential Regulation of Ceruloplasmin Isoforms Expression in Macrophages and...

• Author(s): Marques, L. ; Auriac, A. ; Willemetz, A. ; Banha, J. ; Silva, B. ; Canonne-Hergaux, F. ; Costa, L.
• Date: 2011
• Persistent ID: http://hdl.handle.net/10400.18/224
• Origin: Repositório Científico do Instituto Nacional de Saúde
• Subject(s): Determinantes Imunológicos em Doenças Crónicas; Doenças genéticas
• Document Type: Conference Object
• Language: English

Description

Prémio de melhor poster. Ceruloplasmin (Cp) is an acute-phase protein that has been implicated in iron metabolism due to its ferroxidase activity, assisting ferroportin (Fpn) on cellular iron efflux. However, Cp exhibits both anti- and pro-oxidant activities and its physiological functions remain unclear. Cp can be expressed as a secreted or as a membrane glycosylphosphatidylinositol-anchored protein (GPI-Cp), this latter one being mostly expressed in the brain. Herein, we studied the expression of both Cp isoforms in human peripheral blood lymphocytes, monocytes, mouse macrophages and human hepatocarcinoma cell line HepG2, using immunofluorescence and immunoblotting techniques. Co-localization of Cp and Fpn was also investigated by immunofluorescence in mouse macrophages. Cp was detected by immunoblotting and immunofluorescence in membrane and cytosol of all cells types studied. The Cp detected at cell surface was identified as the GPI-isoform by PI-PLC test and shown to localize in lipid rafts in monocytes, macrophages and HepG2 cells. In macrophages, increased expression levels and co-localization of Fpn and GPI-Cp at cell surface lipid rafts were observed after iron treatment. Such upregulation of Cp by iron was not observed in HepG2 cells. Our results revealed an unexpected ubiquitous expression of the GPI-Cp isoform in immune and hepatic cells. A differential regulation of Cp in these cells may reflect distinct physiological functions of this oxidase according to cell-type specificity. In macrophages, GPI-Cp and Fpn likely interact in lipid rafts to export iron. A better insight into the expression of both Cp isoforms in different cell types will help to clarify its role in many diseases related to iron metabolism, inflammation and oxidative biology.