Dépôt numérique

Syk is a novel target of arsenic trioxide (ATO) and is involved in the toxic effect of ATO in human neutrophils

Antoine, Francis; Ennaciri, Jamila et Girard, Denis ORCID logoORCID: https://orcid.org/0000-0002-3342-5027 (2010). Syk is a novel target of arsenic trioxide (ATO) and is involved in the toxic effect of ATO in human neutrophils Toxicology In Vitro , vol. 24 , nº 3. pp. 936-941. DOI: 10.1016/j.tiv.2009.11.011.

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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. © 2009 Elsevier Ltd. All rights reserved.

Type de document: Article
Mots-clés libres: Arsenic Immunotoxicity Neutrophils Inflammation Syk kinase
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 28 juin 2024 19:17
Dernière modification: 28 juin 2024 19:17
URI: https://espace.inrs.ca/id/eprint/14347

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