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

The cellular prion protein (PrP^C) 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 PrP^C 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 PrP^C), 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 PrP^C to lower intracellular calcium. The lowered calcium concentration and the Caspase 3 downregulation in the PrP^C-null astrocytes resulted in a faster growth rate in cells, comparing with PrP^C wild-type one. The presence of PrP^C 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.