| Syk is a novel target of arsenic trioxide (ATO) and is involved in the toxic effect of ATO in human neutrophils. | |
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MedLine Citation:
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PMID: 19925860 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The anticancer dug arsenic trioxide (ATO) is known to be toxic for human mononuclear and neutrophil cell populations by a mechanism that needs to be further investigated. Due to the well-characterized role of Syk kinase in phagocytosis and because activation and involvement of Syk in response to ATO treatment has never been reported in any cells, we decided to determine whether or not Syk is involved in the mode of action of ATO. Human neutrophils were freshly isolated and incubated in vitro with ATO and the role of Syk was evaluated in different neutrophil functions. We found that ATO increased phosphorylation of Syk and this was reversed by piceatannol, a Syk-specific pharmacological inhibitor. In addition, ATO increased the phagocytic ability of neutrophils and degranulation via Syk activation. Finally, using both pharmacological inhibition and cellular depletion of Syk via an antisense approach, we found that this kinase is involved in apoptosis. We conclude that Syk activation is an important step in the mode of action of ATO in mature immune cells such as neutrophils and is involved in rapid, intermediate and lengthy biological processes. This is the first study to report that Syk is activated by ATO. |
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Authors:
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Francis Antoine; Jamila Ennaciri; Denis Girard |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-16 |
Journal Detail:
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Title: Toxicology in vitro : an international journal published in association with BIBRA Volume: 24 ISSN: 1879-3177 ISO Abbreviation: Toxicol In Vitro Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-03-09 Completed Date: 2010-06-22 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 8712158 Medline TA: Toxicol In Vitro Country: England |
Other Details:
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Languages: eng Pagination: 936-41 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2009 Elsevier Ltd. All rights reserved. |
Affiliation:
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Laboratoire de Recherche en Inflammation et Physiologie des Granulocytes, Université du Québec, INRS-Institut Armand-Frappier, Laval, QC, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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toxicity* Antisense Elements (Genetics) / pharmacology Apoptosis / drug effects Arsenicals Cell Adhesion / drug effects Cell Degranulation / drug effects Cell Separation Enzyme Activation / drug effects Enzyme Inhibitors / pharmacology Humans Intracellular Signaling Peptides and Proteins / antagonists & inhibitors, drug effects* Membrane Proteins / metabolism Neutrophils / drug effects*, enzymology Oxides / toxicity* Phagocytosis / drug effects Phosphorylation Protein-Tyrosine Kinases / antagonists & inhibitors, drug effects* Spleen / drug effects*, enzymology* Stilbenes / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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MOP-89534//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Antisense Elements (Genetics); 0/Arsenicals; 0/Enzyme Inhibitors; 0/Intracellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/Oxides; 0/Stilbenes; 1327-53-3/arsenic trioxide; 4339-71-3/3,3',4,5'-tetrahydroxystilbene; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/Syk kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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