Cellular prion protein activates Caspase 3 for apoptotic defense mechanism in astrocytes.

The cellular prion protein (PrPC) is anchored in the plasma membrane of cells, and it is highly present in cells of brain tissue, exerting numerous cellular and cognitive functions. The present study proves the importance of PrPC in the cellular defense mechanism and metal homeostasis in astrocytes cells. Through experimental studies using cell lines of immortalized mice astrocytes (wild type and knockout for PrPC), we showed that PrPc is involved in the apoptosis cell death process by the activation of Caspase 3, downregulation of p53, and cell cycle maintenance. Metal homeostasis was determined by inductively coupled plasma mass spectrometry technique, indicating the crucial role of PrPC to lower intracellular calcium. The lowered calcium concentration and the Caspase 3 downregulation in the PrPC-null astrocytes resulted in a faster growth rate in cells, comparing with PrPC wild-type one. The presence of PrPC shows to be essential to cell death and healthy growth. In conclusion, our results show for the first time that astrocyte knockout cells for the cellular prion protein could modulate apoptosis-dependent cell death pathways.