Abstract
Tumour necrosis factor (TNF) contributes to the pathogenesis of bone marrow failure in Fanconi anaemia (FA) patients. The sensitivity of haematopoietic cells from FA, complementation group A (FANCA) subjects, who represent the majority of FA patients, to TNF-related apoptosis-inducing ligand (TRAIL) is unknown. The human lymphoblastoid FANCA HSC072 cell line and the genetically corrected counterpart HSC072FANCA-neo were tested for apoptoptic response to TRAIL using flow cytometry and Western blotting. FANCA cells were more sensitive to TRAIL-induced apoptosis than their corrected counterparts, indicating that TRAIL negatively regulates haematopoietic FANCA cell lines. This effect involved poly(ADP-ribose) polymerase-1 cleavage and caspase-8 activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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Biomarkers / analysis
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Caspase 8 / metabolism*
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Caspase Inhibitors
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Cell Line, Tumor
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Enzyme Activation
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Fanconi Anemia / pathology*
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Fanconi Anemia Complementation Group A Protein / analysis
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Fanconi Anemia Complementation Group A Protein / metabolism*
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Fanconi Anemia Complementation Group C Protein / analysis
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Fanconi Anemia Complementation Group C Protein / metabolism
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Humans
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Oligopeptides / pharmacology
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases / analysis
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Poly(ADP-ribose) Polymerases / metabolism
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TNF-Related Apoptosis-Inducing Ligand / pharmacology*
Substances
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Biomarkers
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Caspase Inhibitors
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Fanconi Anemia Complementation Group A Protein
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Fanconi Anemia Complementation Group C Protein
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Oligopeptides
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TNF-Related Apoptosis-Inducing Ligand
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benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone
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PARP1 protein, human
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Poly (ADP-Ribose) Polymerase-1
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Poly(ADP-ribose) Polymerases
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Caspase 8