- E. A. Salvesen
- 7: R225,
Introduction Because of their potential for improved wear performance, there has been a revived interest in metal-metal bearings, made of cobaltchromium-molybdenum alloys, as an alternative to the use of conventional metal-polyethylene bearings. However, metal ion toxicity remains a major cause for concern (1). Indeed, there are multiple sources of metallic corrosion products in the periprosthetic environment. Previous studies demonstrated that both cobalt (Co) and chromium (Cr) ions induced mouse macrophage mortality in a dose-dependent manner (2). The results also suggested that Co and Cr ions induced apoptosis via a pathway involving caspase-3. The interest in apoptosis lies in the fact that it is under positive and negative regulation through evolutionary conserved biochemical pathways that are dependent on the death stimulus and cell context. Therefore, it offers specific targets for therapeutic intervention. The caspase family of proteins plays a central role as initiators and executioners of apoptosis. The first aim of this study was to analyze the effects of Co and Cr ions on the activity of caspase-8 and caspase-3, respectively initiator and executioner of apoptosis, in macrophages. Also, the Bcl-2 family of proteins plays a central role in the modulation of apoptosis. Some of them, such as Bcl-2, protect cells from apoptosis, while others, such as Bax, induce apoptosis. The second aim of the present study was to analyze the effect of Co and Cr ions on the expression of Bcl-2 and Bax to better understand the mechanisms leading to ion-induced apoptosis in macrophages.