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-α (TNF-α) 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-α 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-α 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.