Arsenic trioxide induces endoplasmic reticulum stress-related events in neutrophils

Binet, François; Chiasson, Sonia et Girard, Denis ORCID: https://orcid.org/0000-0002-3342-5027 (2010). Arsenic trioxide induces endoplasmic reticulum stress-related events in neutrophils International Immunopharmacology , vol. 10 , nº 4. pp. 508-512. DOI: 10.1016/j.intimp.2010.01.013.

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Résumé

We recently reported that the endoplasmic reticulum (ER)-induced cell pathway of apoptosis is operational in human neutrophils and that some ER stressors can accelerate this process. Recent data suggest that arsenic trioxide (As₂O₃ or ATO), may also act as an ER stressor. The aims of the present study were to elucidate if other ER stress-related events occur in ATO-induced neutrophils, and to determine the role of caspase-4 in the proapoptotic activity of ATO. We found that ATO induced ubiquitination of proteins, and increased calcium concentration and gene expression of calcineurin in neutrophils. In addition to caspase-4, activities of caspase-3, -8 and -9 were increased by ATO. The processing of caspase-4 was reversed by a caspase-8 inhibitor, indicating that caspase-4 activation requires the action of upstream initiator components, questioning on the role of caspase-4 in ATO-induced ER stress-mediated cell apoptosis. Using caspase-4 deficient THP-1 cells, we demonstrated that the proapoptotic effect of ATO was similar to that of control caspase-4-positive cells. We conclude that ATO is an ER stressor that can induce cell apoptosis by a mechanism which does not require caspase-4. In addition, we conclude that caspase-4 activation in ATO-induced neutrophils could be involved in functions other than apoptosis. © 2010 Elsevier B.V. All rights reserved.

Type de document:	Article
Mots-clés libres:	Arsenic trioxide Neutrophils Apoptosis Ubiquitination Calcium Caspases
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	29 juin 2024 20:41
Dernière modification:	29 juin 2024 20:41
URI:	https://espace.inrs.ca/id/eprint/14417

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