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Cellular prion protein modulates the intracellular calcium response to hydrogen peroxide
Ist Teil von
Journal of neurochemistry, 2007-01, Vol.100 (2), p.358-367
Ort / Verlag
Oxford, UK: Oxford, UK : Blackwell Publishing Ltd
Erscheinungsjahr
2007
Link zum Volltext
Quelle
Wiley-Blackwell Journals
Beschreibungen/Notizen
The physiological function of the cellular prion protein (PrPC) is still under intense investigation. It has been suggested that PrPC has a protective role in neuronal cells, particularly against environmental stress caused by reactive oxygen species (ROS). Here we analysed the acute effect of a major ROS, hydrogen peroxide (H₂O₂), on intracellular calcium homeostasis in cultured cerebellar granule cells and immortalized hippocampal neuronal cells. Both neuronal cell culture models showed that the rise in intracellular calcium following application of H₂O₂ was strongly dependent on the presence of PrPC. Moreover, the N-terminal octapeptide repeats of PrPC were required for this effect, because neuronal cells expressing a PrPC lacking the N-terminus resembled the PrPC-deficient phenotype. Neurones deficient of fyn kinase, or pharmacological inhibition of fyn, also abrogated the calcium response to H₂O₂ treatment, indicating that fyn activation is a critical step within the PrPC signalling cascade. Finally, we identified a possible role of this PrPC signalling pathway in the neuroprotective response of PrPC to oxidative stress. In conclusion, we put forward the hypothesis that PrPC functions as a sensor for H₂O₂, thereby activating a protective signalling cascade involving fyn kinase that leads to calcium release from intracellular stores.