Tumor necrosis factor attenuates prion protein-deficient neuronal cell death by increases in anti-apoptotic Bcl-2 family proteins.
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.
Sakudo
Akikazu
A
Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Japan.
Lee
Deug-Chan
DC
Saeki
Keiichi
K
Matsumoto
Yoshitsugu
Y
Itohara
Shigeyoshi
S
Onodera
Takashi
T
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016923:Cell Death; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005434:Flow Cytometry; D051379:Mice; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000166:cytology*; D010957:Plasmids / Q000378:metabolism; D011328:Prions / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D018076:DNA, Complementary; D011328:Prions; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein