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Anti-apoptotic properties of physiological and elevated levels of the cellular prion protein (PrP c ) under stress conditions are well documented. Yet, detrimental effects of elevated PrP c  levels under stress conditions, such as exposure to staurosporine (STS) have also been described. In the present study, we focused on discerning early apoptotic STS-induced proteome and phospho-proteome changes in SH-SY5Y human neuroblastoma cells stably transfected either with an empty or  PRNP -containing vector, expressing physiological or supraphysiological levels of PrP c , respectively. PrP c -overexpression  per se  appears to stress the cells under STS-free conditions as indicated by diminished cell viability of PrP c -overexpressing  versus  control cells. However, PrP c -overexpression becomes advantageous following exposure to STS. Thus, only a short exposure (2 h) to 1  μ M STS results in lower survival rates and significantly higher caspase-3 activity in control  versus  PrP c -overexpressing cells. Hence, by exposing both experimental groups to the same apoptotic conditions we were able to induce apoptosis in control, but not in PrP c -overexpressing cells (as assessed by caspase-3 activity), which allowed for filtering out proteins possibly contributing to protection against STS-induced apoptosis in PrP c -overexpressing cells. Among other proteins regulated by different PrP c  levels following exposure to STS, those involved in maintenance of cytoskeleton integrity caught our attention. In particular, the finding that elevated PrP c  levels significantly reduce profilin-1 (PFN-1) expression. PFN-1 is known to facilitate STS-induced apoptosis. Silencing of PFN-1 expression by siRNA significantly increased viability of PrP c -overexpressing  versus  control cells, under STS treatment. In addition, PrP c -overexpressing cells depleted of PFN-1 exhibited increased viability  versus  PrP c -overexpressing cells with preserved PFN-1 expression, both subjected to STS. Concomitant increase in caspase-3 activity was observed in control  versus  PrP c -overexpressing cells after treatment with siRNA- PFN-1 and STS. We suggest that reduction of PFN-1 expression by elevated levels of PrP c  may contribute to protective effects PrP c -overexpressing SH-SY5Y cells confer against STS-induced apoptosis.

Cellular prion protein mediates early apoptotic proteome alternation and phospho-modification in human neuroblastoma cells