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Involvement of CD45 in DNA fragmentation in apoptosis induced by mitochondrial perturbing agents

Desharnais, Philippe; Dupéré-Minier, Geneviève; Hamelin, Claudine; Devine, Patrick et Bernier, Jacques ORCID logoORCID: https://orcid.org/0000-0002-0594-5922 (2008). Involvement of CD45 in DNA fragmentation in apoptosis induced by mitochondrial perturbing agents Apoptosis , vol. 13 , nº 2. pp. 197-212. DOI: 10.1007/s10495-007-0162-9.

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Résumé


CD45 is a type I transmembrane molecule with phosphatase activity which comprises up to 10% of the cell surface area in nucleated haematopoietic cells. We have previously demonstrated the absence of nuclear apoptosis in CD45-negative T cells after chemical-induced apoptosis. The aim of this study was to characterize the role of CD45 in nuclear apoptosis. In contrast to wild type CD45-positive T cells, the CD45-deficient T cell lines are resistant to the induction of DNA fragmentation and chromatin condensation following tributyltin (TBT) or H2O2 exposure, but not to cycloheximide-induced apoptosis. CD45 transfection in deficient cell lines led to the restoration of chromatin condensation and DNA fragmentation following TBT exposure. In both CD45-positive and negative T cell lines, TBT exposure mediates intracellular calcium mobilization, caspase-3 activation and DFF45 cleavage. Moreover, DNA fragmentation was also induced by TBT in cells deficient in expression of p56lck, ZAP-70 and SHP-1. Subcellular partitioning showed a decrease in nuclear localisation of caspase-3 and DFF40. Together, these results demonstrate for the first time, that CD45 expression plays a key role in internucleosomal DNA fragmentation and chromatin condensation processes during apoptosis. CD45 activity or its substrates' activity, appears to be located downstream of caspase-3 activation and plays a role in retention of DFF40 in the nucleus.

Type de document: Article
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 21 juill. 2024 19:01
Dernière modification: 21 juill. 2024 19:01
URI: https://espace.inrs.ca/id/eprint/14589

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