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

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Abstract

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.

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Acknowledgments

This work was supported by NSERC: Natural Sciences and Engineering Research Council of Canada. We are grateful to Drs. Michel Tremblay and Pascal Duplay for the cell lines.

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  1. INRS-Institut Armand-Frappier, 531 boul. des Prairies, Laval, QC, Canada, H7V 1B7

    Philippe Desharnais, Geneviève Dupéré-Minier, Claudine Hamelin, Patrick Devine & Jacques Bernier

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  1. Philippe Desharnais
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  2. Geneviève Dupéré-Minier
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  3. Claudine Hamelin
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  4. Patrick Devine
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  5. Jacques Bernier
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Correspondence to Jacques Bernier.

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Philippe Desharnais and Geneviève Dupéré-Minier have contributed equally to this work.

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Desharnais, P., Dupéré-Minier, G., Hamelin, C. et al. Involvement of CD45 in DNA fragmentation in apoptosis induced by mitochondrial perturbing agents. Apoptosis 13, 197–212 (2008). https://doi.org/10.1007/s10495-007-0162-9

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