Interferon γ Induces Upregulation and Activation of Caspases 1, 3, and 8 to Produce Apoptosis in Human Erythroid Progenitor Cells

摘要: Interferon γ (IFNγ) induces apoptosis in purified human erythroid colony-forming cells (ECFC) and inhibits cell growth. Fas (APO-1; CD95) ligand (FasL) mediate induced by IFNγ, because is significantly upregulated whereas constitutively present the ECFC neutralization of FasL greatly reduces apoptosis. Because conversion caspases from their dormant proenzyme forms to active enzymes has a critical role transducing cascade leading apoptosis, we performed further studies expression activation normal IFNγ-treated day-6 better understand mechanism IFNγ action producing this death. RNase protection assays showed that caspase-1, -2, -6, -8, -9 mRNAs were caspase-5 -7 not increased. Western blots FLICE/caspase-8 was activated 24 hours incubation with IFNγ. FADD similarly altered ICE/caspase-1, which might be required for amplification initial FLICE signal, pro-ICE increased after treatment cleavage also CPP32/apopain/caspase-3, responsible proteolytic poly (ADP) ribose polymerase (PARP), studied resulted an concentration caspase-3 clear induction enzyme 48 hours, identified appearance its p17-kD peptide fragment. The PARP demonstrated obvious increase 89-kD product, observed at almost same time as cells, untreated little change. Peptide inhibitors caspase proteins, DEVD-fmk, DEVD-cho, YVAD-cho, IETD-fmk, incubated obtain evidence involvement IFNγ-induced CPP32/caspase-3 clearly inhibited, but reduction growth due only partially blocked presence inhibitors. These results indicate acts on upregulate Fas, selectively caspases-1, -3, are produce concentrations demonstrably changed.