Involvement of CD45 in DNA fragmentation in apoptosis induced by mitochondrial perturbing agents |
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Authors: | Philippe Desharnais Geneviève Dupéré-Minier Claudine Hamelin Patrick Devine Jacques Bernier |
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Institution: | (1) INRS-Institut Armand-Frappier, 531 boul. des Prairies, Laval, QC, Canada, H7V 1B7 |
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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.
Philippe Desharnais and Geneviève Dupéré-Minier have contributed equally to this work. |
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Keywords: | Lymphoma CD45 DNA fragmentation Nuclear apoptosis TBT Mitochondrial perturbating agent DFF40 DFF45 |
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