Document Detail

Gene expression changes induced by bismuth in a macrophage cell line.
MedLine Citation:
PMID:  15912405     Owner:  NLM     Status:  MEDLINE    
We have investigated the effect of bismuth by autometallography, cell viability, TUNEL assay and microarray analysis of a macrophage cell line. The cells accumulate bismuth in their lysosomes in a time- and dose-dependent manner. Cell viability assays show a significant decrease in the number of viable cells related to both bismuth concentrations and exposure time. TUNEL assays after 12 h and 24 h at a bismuth-citrate concentration of 50 microM revealed the presence of 30% and 70% TUNEL-positive cells, respectively, compared with 8% in the controls. We have analysed gene expression profiles for cells exposed to 50 microM bismuth-citrate and for untreated controls at 12 h and 24 h by microarray analysis, which confirmed that bismuth is a powerful metallothionein inducer. A number of glycolytic enzymes are induced by bismuth, suggesting that bismuth is able to induce "hypoxia-like" stress. BCL2/adenovirus E1B 19-kDa-interacting protein 3 (Bnip3) has been suggested as a regulator of hypoxia-induced cell death independent of caspase-3 activation and cytochrome c release. Bnip3 is up-regulated indicating the involvement of Bnip3 as a possible mechanism for bismuth-induced cell death. Differences have been noticed in cell viability and in the modification of the mRNA expression levels at 12 and 24 h. Only 13 genes are modified at both these times, suggesting a time-dependent molecular cascade in which bismuth-exposed cells enter a dormant stage with mRNA down-regulation being followed by cell death of susceptible cells.
Nils E Magnusson; Agnete Larsen; Jørgen Rungby; Mogens Kruhøffer; Torben F Orntoft; Meredin Stoltenberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-05-24
Journal Detail:
Title:  Cell and tissue research     Volume:  321     ISSN:  0302-766X     ISO Abbreviation:  Cell Tissue Res.     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-07-19     Completed Date:  2006-01-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0417625     Medline TA:  Cell Tissue Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  195-210     Citation Subset:  IM    
Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital, Denmark.
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MeSH Terms
Apoptosis / drug effects*,  physiology
Bismuth / metabolism,  toxicity*
Cell Line
Cell Survival / drug effects,  physiology
Dose-Response Relationship, Drug
Down-Regulation / drug effects,  physiology
Enzyme Activation / drug effects,  physiology
Gene Expression Regulation, Enzymologic / drug effects,  physiology
In Situ Nick-End Labeling
Lysosomes / drug effects,  metabolism
Macrophages / drug effects*,  metabolism
Membrane Proteins / drug effects,  genetics,  metabolism
Oxidative Stress / drug effects,  physiology
Proto-Oncogene Proteins / drug effects,  genetics,  metabolism
RNA, Messenger / drug effects,  metabolism
Time Factors
Up-Regulation / drug effects,  physiology
Reg. No./Substance:
0/BNIP3 protein, human; 0/Membrane Proteins; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 7440-69-9/Bismuth

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