Effect of cobalt and chromium ions on bcl-2, bax, caspase-3, and caspase-8 expression in human U937 macrophages

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Title: Effect of cobalt and chromium ions on bcl-2, bax, caspase-3, and caspase-8 expression in human U937 macrophages
Authors: Petit, Alain1, Mwale, Fackson1, Zukor, David J.1, Catelas, Isabelle1, Antoniou, John1, Huk, Olga L. ohuk@ldi.jgh.mcgill.ca
Source: Biomaterials. May2004, Vol. 25 Issue 11, p2013. 6p.
Subjects: Proteins, Metal ions, Chromium, Apoptosis
Abstract: The bcl-2 and caspase families of proteins play a central role in the modulation of apoptosis. The purpose of this study was to analyze the effect of Co2+ and Cr3+ ions on the expression of bcl-2, bax, caspase-3 and caspase-8 to better understand the mechanisms leading to ion-induced apoptosis in macrophages. U937 human macrophages were exposed to Co2+ and Cr3+ ions. The expression of proteins was measured by Western blot while caspase activities were measured by colorimetric assay. Results show that Co2+ ions inhibited bcl-2 expression with significant effect (p<0.05) after 16 h and a maximal 52% inhibitory effect after 24 h. Co2+ stimulated bax expression with a significant stimulation (p<0.05) after 8 h and a maximal 1.75-fold increase after 16 h. Co2+ also stimulated the expression of the active fragment of caspase-3 as well as caspase-3 activity maximal increase after 24 h. Co2+ ions had no effect on caspase-8 expression or activity.Cr3+ ions inhibited bcl-2 expression with significant effect (p<0.05) after 16 h and a maximal 43% inhibitory effect after 24 h. Cr3+ stimulated bax expression with significant stimulation (p<0.01) after 8 h and a maximal 2.25-fold increase after 24 h. Cr3+ ions also stimulated the expression of the active fragments of caspase-3 and -8, as well as the activities of both proteases. The effect of Cr3+ ions on the expression of both caspase active fragments was maximal after 16 h incubation. In conclusion, our results suggest that the modulation of the expression of proteins from the bcl-2 and the caspase families of proteins are implicated in the induction of macrophage apoptosis by Co2+ and Cr3+ ions. [Copyright &y& Elsevier]
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Abstract:The bcl-2 and caspase families of proteins play a central role in the modulation of apoptosis. The purpose of this study was to analyze the effect of Co2+ and Cr3+ ions on the expression of bcl-2, bax, caspase-3 and caspase-8 to better understand the mechanisms leading to ion-induced apoptosis in macrophages. U937 human macrophages were exposed to Co2+ and Cr3+ ions. The expression of proteins was measured by Western blot while caspase activities were measured by colorimetric assay. Results show that Co2+ ions inhibited bcl-2 expression with significant effect (<f>p<0.05</f>) after 16 h and a maximal 52% inhibitory effect after 24 h. Co2+ stimulated bax expression with a significant stimulation (<f>p<0.05</f>) after 8 h and a maximal 1.75-fold increase after 16 h. Co2+ also stimulated the expression of the active fragment of caspase-3 as well as caspase-3 activity maximal increase after 24 h. Co2+ ions had no effect on caspase-8 expression or activity.Cr3+ ions inhibited bcl-2 expression with significant effect (<f>p<0.05</f>) after 16 h and a maximal 43% inhibitory effect after 24 h. Cr3+ stimulated bax expression with significant stimulation (<f>p<0.01</f>) after 8 h and a maximal 2.25-fold increase after 24 h. Cr3+ ions also stimulated the expression of the active fragments of caspase-3 and -8, as well as the activities of both proteases. The effect of Cr3+ ions on the expression of both caspase active fragments was maximal after 16 h incubation. In conclusion, our results suggest that the modulation of the expression of proteins from the bcl-2 and the caspase families of proteins are implicated in the induction of macrophage apoptosis by Co2+ and Cr3+ ions. [Copyright &y& Elsevier]
ISSN:01429612
DOI:10.1016/j.biomaterials.2003.08.040