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Cytotoxic and apoptotic effects of cobalt and chromium ions on J774 macrophages - Implication of caspase-3 in the apoptotic pathway.
MedLine Citation:
PMID:  15348346     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
The aim of this study was to evaluate the cytotoxic and apoptotic effects of cobalt and chromium ions on macrophages in vitro, and analyze the implication of caspase-3 in the apoptotic pathway. J774 mouse macrophages (5 x 10(5) cells/ml) were exposed for up to 24 h to 0-10 ppm Co2+ and 0-500 ppm Cr3+. The cytotoxic effect of ions was measured by Trypan blue exclusion. DNA analysis on agarose gel was used as a specific test for detection of DNA fragmentation into oligonucleosomes that occurs in apoptotic cells. The proteolytic cleavage of poly(ADP-ribose)polymerase (PARP), closely associated with the induction of apoptosis, was also analyzed along with the appearance of the active fragment of caspase-3, implicated in several apoptosis pathways. Results demonstrated that both Co2+ and Cr3+ ions induce macrophage mortality in a dose-dependent manner. However, Co2+ is more toxic inducing a cell mortality up to 28% with only 10 ppm vs. 37% with 500 ppm of Cr3+. DNA analysis demonstrated that both Co2+ and Cr3+ ions induce DNA fragmentation, between 6-10 ppm Co2+ and 250-500 ppm Cr3+ after 24 h incubation. PARP cleavage and the appearance of caspase-3 active fragment were observed after 6 h with both Co+ and Cr3+ ions, with a stronger signal after 24 h and 10 ppm of Co2+ or 500 ppm of Cr3+. In conclusion, this study demonstrates that after 24 h incubation, both Co2+ and Cr3+ ions can induce macrophage mortality, and more specifically apoptosis. The results also suggest that apoptosis occurs via a caspase-3 pathway. However, the relative importance of necrosis and apoptosis and the effects of longer exposure times on the induction of macrophage death by these metal ions remain to be investigated.
Authors:
I Catelas; A Petit; D J Zukor; O L Huk
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of materials science. Materials in medicine     Volume:  12     ISSN:  0957-4530     ISO Abbreviation:  J Mater Sci Mater Med     Publication Date:    2001 Oct-Dec
Date Detail:
Created Date:  2004-09-06     Completed Date:  2005-03-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9013087     Medline TA:  J Mater Sci Mater Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  949-53     Citation Subset:  -    
Copyright Information:
Copyright 2001 Kluwer Academic Publishers
Affiliation:
Department of Biomedical Engineering, McGill University, Duff Medical Building, 3775 University Street, Montreal, Quebec, Canada, H3A 2B4.
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