The PrP(C) protein, which is especially present in the cellular membrane of nervous system cells, has been extensively studied for its controversial antioxidant activity. In this study, we elucidated the free radical scavenger activity of purified murine PrP(C) in solution and its participation as a cell protector in astrocytes that were subjected to treatment with an oxidant. In vitro and using an EPR spin-trapping technique, we observed that PrP(C) decreased the oxidation of the DMPO trap in a Fenton reaction system (Cu(2+)/ascorbate/H(2)O(2)), which was demonstrated by approximately 70% less DMPO/OH(). In cultured PrP(C)-knockout astrocytes from mice, the absence of PrP(C) caused an increase in intracellular ROS (reactive oxygen species) generation during the first 3h of H(2)O(2) treatment. This rapid increase in ROS disrupted the cell cycle in the PrP(C)-knockout astrocytes, which increased the population of cells in the sub-G1 phase when compared with cultured wild-type astrocytes. We conclude that PrP(C) in solution acts as a radical scavenger, and in astrocytes, it is essential for protection from oxidative stress caused by an external chemical agent, which is a likely condition in human neurodegenerative CNS disorders and pathological conditions such as ischemia.
Background: In addition to the toxicity mediated by prion protein misfolding, mechanisms associated with its loss-offunction in genetic prion diseases are unknown. Results: Neural cells expressing PrP C mutants associated with prion diseases present impaired laminin-mediated process outgrowth and survival. Conclusion: PrP C mutants show loss-of-function in neural cells. Significance: The impairment of prion protein functions may contribute to the etiology of prion diseases.
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