Physiological role of the cellular prion protein (PrPc): Protein profiling study in two cell culture systems

The physiological role of the cellular prion protein (PrPc) is still not fully understood. Current evidence strongly suggests that PrPc overexpression in different cell lines sensitizes cells to apoptotic stimuli through a p53 dependent pathway. On the other hand, an expression of PrPc in PrPc-deficient cells undergoing apoptosis exhibited repeatedly antiapoptotic effects. Therefore, the presence/absence and/ or the level of PrPc expression seem to be critical for the fluctuation between PrPc's pro- and antiapoptotic properties. The present study examined whether an overexpression of PrPc itself, without addition of any apoptotic agent, can lead to proteome changes that might account for the higher responsiveness to apoptotic stimuli. Beyond this, we examined whether the sole introduction of PrPc into PrPc-deficient cells could be sufficient to up-regulate antiapoptotic proteins capable of mitigating apoptosis. For this purpose, we used two cell lines, one expressing [human embryonic kidney (HEK) 293 cells] and the other lacking (mouse neuronal PrPc-deficient cells) endogenous PrPc. Protein profiling following transient PrPc overexpression in HEK 293 cells revealed a major PrPc involvement in regulation of proteins participating in energy metabolism and cellular homeostasis, whereas transient introduction of PrPc into mouse neuronal PrPc-deficient cells resulted mainly in the regulation of proteins involved in protection against oxidative stress and apoptosis. In addition, we report for the first time that PrPc overexpression influenced the regulation of several proteins known to have contributory roles in the pathogenesis of Alzheimer disease (AD). Revealing the correlation between presence/absence and/or different levels of PrPc expression with the regulation of certain cellular proteins might further contribute to our understanding of the complex role of PrPc in cell physiology.