부산대학교 도서관

Sae-ung N, Matsushima T, Choi I, Abe Y, Winichagoon P, Fucharoen S, Nawata H, Muta K. Role of NF-κB in regulation of apoptosis of erythroid progenitor cells.Eur J Haematol 2005: 74: 315–323.© Blackwell Munksgaard 2005.Erythropoietin (EPO) and interferon-γ (IFN-γ) added to human erythroid progenitor cells purified from peripheral blood (erythroid colony-forming cells; ECFC) significantly reduces apoptosis as assessed by flow cytometry(FCM) using annexin V. To clarify the role of NF-κB in the regulation of the apoptosis of erythroid progenitor cells, cyclosporin A (CsA), which blocks dissociation of the NF-κB complex, was added to serum-free cultures of ECFC. CsA induced the apoptosis of ECFCs in the presence of EPO or IFN-γ, but at different magnitudes. In the presence of a relatively low concentration of CsA (10 μm), apoptosis was induced only in cultures with EPO. The direct involvement of NF-κB was then assessed by Western blotting and confocal microscopy. In the presence of EPO, NF-κB was abundant both in the cytoplasm and in the nucleus, and nuclear expression was diminished after adding CsA. In contrast, NF-κB was undetectable in the nucleus in the presence of IFN-γ. The effect of CsA on mitochondrial function was investigated by determining theΔΨm and reactive oxygen species production. CsA disturbed the transmembrane potential in the presence of either EPO or IFN-γ, although the viability of the cells was maintained in the presence of IFN-γ plus CsA. These results indicate that IFN-γ reduced the apoptosis of erythroid progenitor cells through a unique signaling pathway that is independent of NF-κB translocation, and which is not mediated by modulating mitochondrial function, whereas EPO reduced apoptosis through NF-κB translocation to the nucleus. [ABSTRACT FROM AUTHOR]