Human Fanconi A cells are susceptible to TRAIL-induced apoptosis

Br J Haematol. 2007 Jan;136(2):315-8. doi: 10.1111/j.1365-2141.2006.06432.x.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Biomarkers / analysis
  • Caspase 8 / metabolism*
  • Caspase Inhibitors
  • Cell Line, Tumor
  • Enzyme Activation
  • Fanconi Anemia / pathology*
  • Fanconi Anemia Complementation Group A Protein / analysis
  • Fanconi Anemia Complementation Group A Protein / metabolism*
  • Fanconi Anemia Complementation Group C Protein / analysis
  • Fanconi Anemia Complementation Group C Protein / metabolism
  • Humans
  • Oligopeptides / pharmacology
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / analysis
  • Poly(ADP-ribose) Polymerases / metabolism
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*

Substances

  • Biomarkers
  • Caspase Inhibitors
  • Fanconi Anemia Complementation Group A Protein
  • Fanconi Anemia Complementation Group C Protein
  • Oligopeptides
  • TNF-Related Apoptosis-Inducing Ligand
  • benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Caspase 8