| Role of zinc ions in ricin-induced apoptosis in U937 cells. | |
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MedLine Citation:
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PMID: 12044548 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Tadashi Tamura; Noriko Sadakata; Tatsuya Oda; Tsuyoshi Muramatsu |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Toxicology letters Volume: 132 ISSN: 0378-4274 ISO Abbreviation: Toxicol. Lett. Publication Date: 2002 Jun |
Date Detail:
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Created Date: 2002-06-04 Completed Date: 2002-07-16 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 7709027 Medline TA: Toxicol Lett Country: Netherlands |
Other Details:
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Languages: eng Pagination: 141-51 Citation Subset: IM |
Affiliation:
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Division of Biochemistry, Faculty of Fisheries, Nagasaki University, Bunkyo-machi 1-14, Nagasaki 852-8521, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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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:
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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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