Document Detail


Role of zinc ions in ricin-induced apoptosis in U937 cells.
MedLine Citation:
PMID:  12044548     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We found that treatment of U937 cells with ZnCl(2) resulted in marked inhibition of ricin-induced DNA fragmentation and nuclear morphological change. Zn(2+) also completely inhibited the activation of caspase-3-, caspase-6-, and caspase-9-like proteases in ricin-treated cells, while no significant effect of Zn(2+) on these protease activities was observed when added directly to the lysate of ricin-treated cells, suggesting that Zn(2+) blocks the process of the activation of these caspases rather than the direct inhibition of the already activated enzymes. Fluorescence microscopic observation with Zn(2+) specific fluorescent probe dansylaminoethyl-cyclen suggested that there was a substantial increase in probe-detectable Zn(2+) in ricin-treated cells. Since the differences in the total Zn(2+) contents between ricin-treated and -untreated cells as measured with an atomic absorption spectrophotometer were too small to explain the increase in probe fluorescence in ricin-treated cells, it was suggested that release of Zn(2+) from intracellular stores or metalloproteins may occur rather than enhanced uptake from the medium. The Zn(2+) probe fluorescence change was observed prior to the depletion of intracellular glutathione. Carbobenzoxy-Asp-1-yl-[(2,6-dichlorobenzoyl)oxy]methane (Z-Asp-CH(2)-DCB), a caspase family protease inhibitor, prevented ricin-induced increase in Zn(2+) probe fluorescence. These results suggest that redistribution of intracellular Zn(2+) occurs during ricin-induced apoptosis as early apoptotic event, and exogenously added Zn(2+) may prevent such intracellular Zn(2+) redistribution resulting in the inhibition of apoptosis.
Authors:
Tadashi Tamura; Noriko Sadakata; Tatsuya Oda; Tsuyoshi Muramatsu
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Toxicology letters     Volume:  132     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-06-04     Completed Date:  2002-07-16     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  141-51     Citation Subset:  IM    
Affiliation:
Division of Biochemistry, Faculty of Fisheries, Nagasaki University, Bunkyo-machi 1-14, Nagasaki 852-8521, Japan.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Astringents / therapeutic use*
Caspases / drug effects,  metabolism
DNA Fragmentation / drug effects
Humans
Ricin / antagonists & inhibitors*,  toxicity
U937 Cells
Zinc Sulfate / therapeutic use*
Chemical
Reg. No./Substance:
0/Astringents; 7733-02-0/Zinc Sulfate; 9009-86-3/Ricin; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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