system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Apoptosis, Apoptosis Regulatory Proteins, CASP8 and FADD-Like Apoptosis Regulating Protein, Carrier Proteins, Caspase 8, Caspases, Cell Cycle Proteins, DNA-Binding Proteins, Fanconi Anemia, Fanconi Anemia Complementation Group C Protein, Fanconi Anemia Complementation Group Proteins, Gene Expression Profiling, Hematopoietic Stem Cells, Humans, Intracellular Signaling Peptides and Proteins, Membrane Glycoproteins, Mice, Nuclear Proteins, Proteins, Signal Transduction, TNF-Related Apoptosis-Inducing Ligand, Tumor Necrosis Factor-alpha.
user
Are fanconi anemia type C-deficient hematopoietic cells resistant to TRAIL ( TNF-related apoptosis-inducing ligand ) -induced cleavage of pro-caspase-8? Context: The pathophysiology of bone marrow failure in Fanconi anemia (FA) patients is thought to involve excessive apoptosis involving signaling triggered by fas ligation and tumor necrosis factor (TNF)-alpha, or interferon (IFN)-gamma exposure. We investigated whether a new member of the TNF family, TRAIL (TNF-related apoptosis-inducing ligand), would similarly trigger preferential apoptotic cell death in FA phenotype cells. Hematopoietic cells from FANCC(-/-) transgenic mice and human FA-C lymphoblasts (HSC536N) as well as their phenotypically corrected counterparts (FANCC(+/+), HSC536/FA-Cneo) were compared for their response to apoptosis induction by TRAIL and fas ligation in the presence or absence of IFN-gamma. Cells were also studied for the protein and gene expression of TRAIL-receptors, caspase-8 and its inhibitory protein, FLIP. TRAIL exposure by itself or in combination with IFN-gamma did not lead to preferential apoptosis induction in human and murine FA-C phenotype hematopoietic cells. This resistance was unrelated to the expression of TRAIL receptors or FLIP isoforms, but correlated with absent cleavage of pro-caspase-8. Results were validated by those from gene expression profiling of relevant genes in the two lymphoblast cell lines.
assistant
TRAIL, in contrast to fas ligation, does not induce preferential apoptosis in FA-C phenotype cells despite shared downstream signaling described in non-FA models. These data provide further insight into the complexity of FA-C-regulated apoptotic signaling. Final Decision: yes