Apoptotic volume decrease, pH acidification and chloride channel activation during apoptosis requires CD45 expression in HPB-ALL T cells.
Mitochondrial-perturbating agents such as toxic coumponds induce apoptosis. We note that the loss of CD45 expression in the lymphoblastic leukemia cell line HPB-ALL (HPB45.0) leads to an inhibition of nuclear apoptosis. Our hypothesis is that the absence of CD45 disturbs protein function regulated by a proto-oncogene of the Src family playing a significant role in nuclear apoptosis. In this work we explore the importance of a chloride efflux on DNA fragmentation. The role of tyrosine kinase in the function and regulation of the chloride channels was determined. Our results showed a disturbance of ionic homeostasis in CD45 deficient lymphocytes (CD45-) in contrast to normal lymphocytes (CD45+). The phosphorylation levels of the chloride channels are considerably inhibited in CD45-, while the expression levels of these channels are similar in the two types of cells. A hypertonic medium inhibits DNA fragmentation in CD45+ while a hypotonic medium increases DNA fragmentation in CD45-. Thus CD45 plays a significant role in nuclear apoptosis by the regulation of the chloride channels responsible for ionic homeostasis of the cell essential for the DFF40 activation.
INRS-Institut Armand-Frappier, Pointe-Claire, Quebec H9R 1G6, Canada.
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Dupéré-Minier
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Hamelin
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Desharnais
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Bernier
D015703:Antigens, CD / Q000235:genetics / Q000502:physiology; D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000502:physiology / Q000648:ultrastructure; D048429:Cell Size; D018118:Chloride Channels / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology / Q000473:pathology*; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000502:physiology*; D010718:Phosphatidylserines / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D000090063:Proto-Oncogene Mas
D015703:Antigens, CD; D018118:Chloride Channels; C000715470:MAS1 protein, human; D010718:Phosphatidylserines; D000090063:Proto-Oncogene Mas; D011505:Protein-Tyrosine Kinases; D017493:Leukocyte Common Antigens