title: Induction of protein oxidation by cobalt and chromium ions in human U937 macrophages.
abstract: Metal particles and ions from hip prostheses have the potential to induce the production of reactive oxygen species (ROS), making them prime suspects for disturbing the cellular balance of oxidants/antioxidants (redox state of the cell). To better understand the cellular effect of metal ions from metal-on-metal prostheses, the aim of this study was to examine the effect of cobalt (Co2+) and chromium (Cr3+) ions on protein oxidation in human U937 macrophages. Protein oxidation was measured by Western blot using antibodies directed against dinitrophenylhydrazine (DNP)-derivatized protein carbonyls, the most commonly measured products of protein oxidation in biological samples. Three DNP-derived proteins were detected. The first has a molecular weight of 16 kDa and is expressed at a very low level. The second has a molecular weight of 48 kDa and its level is not regulated by metal ions. The third is a 69 kDa protein and its level is regulated by Co2+ and Cr3+ ions. Therefore, the last band served as a marker of protein oxidation in the present study. Results showed that Co2+ and Cr3+ ions induced a time- and dose-dependent protein oxidation reaching 6.5 and 2.9 times the control after 72 h, respectively, which were inhibited by the antioxidant glutathione monoethyl-ester. Finally, results showed that the oxidized proteins are mainly found in the cytoplasmic fraction of the cells and are absent from the nucleus. In conclusion, our results suggest that metal ions from metal-on-metal prostheses have the potential to modify the redox state of cells both locally (periprosthetic environment) or systematically (circulating cells). The long term effect of these ions on protein oxidation in vivo remains to be investigated.
authors.affiliation: Division of Orthopaedic Surgery, Lady Davis Institute for Medical Research, McGill University, The SMBD-Jewish General Hospital, 3755 Ch. Cote Ste-Catherine, Montreal, Quebec, Canada H3T 1E2.
authors.forename: Alain
authors.initials: A
authors.lastname: Petit
authors.forename: Fackson
authors.initials: F
authors.lastname: Mwale
authors.forename: Cathy
authors.initials: C
authors.lastname: Tkaczyk
authors.forename: John
authors.initials: J
authors.lastname: Antoniou
authors.forename: David J
authors.initials: DJ
authors.lastname: Zukor
authors.forename: Olga L
authors.initials: OL
authors.lastname: Huk
mesh_terms: D001672:Biocompatible Materials / Q000494:pharmacology*; D002857:Chromium / Q000494:pharmacology*; D003035:Cobalt / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006622:Hip Prosthesis / Q000009:adverse effects; D006801:Humans; D007477:Ions; D008422:Materials Testing; D010084:Oxidation-Reduction / Q000187:drug effects*; D011475:Prosthesis Failure; D011506:Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020298:U937 Cells
chemical_list: D001672:Biocompatible Materials; D007477:Ions; D011506:Proteins; D017382:Reactive Oxygen Species; D002857:Chromium; D003035:Cobalt