NR APLI
AU Sakudo,A.; Lee,D.C.; Saeki,K.; Matsumoto,Y.; Itohara,S.; Onodera,T.
TI Tumor necrosis factor attenuates prion protein-deficient neuronal cell death by increases in anti-apoptotic Bcl-2 family proteins
QU Biochemical and Biophysical Research Communications 2003 Oct 24; 310(3): 725-9
PT journal article
AB Prion protein gene (Prnp)-deficient(Prnp(-/-)) neuronal cells are more susceptible to serum deprivation compared to Prnp(+/+) neuronal cells. However, little is known about the cell death of Prnp(-/-) neuronal cells under serum deprivation. In this study, as a known neuroprotective agent we analyzed the effect of tumor necrosis factor-alpha (TNF-alpha) on the cell death of Prnp(-/-) neuronal cells. Although expression of Bcl-2 and Bcl-x(L) decreased in a time-dependent manner under serum deprivation, treatment with TNF-alpha protected Prnp(-/-) neuronal cells from serum deprivation with an increase in anti-apoptotic proteins Bcl-2 and Bcl-x(L). Nuclear morphological analysis using fluorescence microscopy and flow cytometry analysis showed that gene transfer of bcl-2 or bcl-x(L) significantly inhibited apoptosis induced by serum deprivation. These findings indicate that TNF-alpha attenuated cell death of Prnp(-/-) neuronal cells by induction of Bcl-2 and Bcl-x(L),and that decreases in Bcl-2 and Bcl-x(L) played crucial roles in the apoptosis of Prnp(-/-) neuronal cells.
MH Animals; *Apoptosis; Blotting, Western; Cell Death; Cell Line; Cell Nucleus/metabolism; Cell Survival; DNA, Complementary/metabolism; Dose-Response Relationship, Drug; Down-Regulation; Flow Cytometry; Mice; Microscopy, Fluorescence; Neurons/*cytology; Plasmids/metabolism; Prions/*metabolism; Proto-Oncogene Proteins c-bcl-2/*metabolism; Support, Non-U.S. Gov't; Time Factors; Tumor Necrosis Factor/metabolism/*physiology
AD Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Japan.
SP englisch
PO USA