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Selective prion protein binding to synaptic components is modulated by oxidative and nitrosative changes induced by copper(II) and peroxynitrite in cholinergic synaptosomes, unveiling a role for calcineurin B and thioredoxin
Author(s) -
MorotGaudryTalarmain Y.,
Rezaei H.,
Guermonprez L.,
Treguer E.,
Grosclaude J.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02111.x
Subject(s) - peroxynitrite , oxidative phosphorylation , chemistry , biochemistry , cholinergic , microbiology and biotechnology , biophysics , biology , neuroscience , enzyme , superoxide
Choline acetyltransferase (ChAT) and choline transport are decreased after nitrosative stress. ChAT activity is altered in scrapie‐infected neurons, where oxidative stress develops. Cellular prion protein (PrP c ) may play a neuroprotective function in participating in the redox control of neuronal environment and regulation of copper metabolism, a role impaired when PrP c is transformed into PrP Sc in prion pathologies. The complex cross‐talk between PrP c and cholinergic neurons was analyzed in vitro using peroxynitrite and Cu 2+ treatments on nerve endings isolated from Torpedo marmorata , a model of the motoneuron pre‐synaptic element. Specific interactions between solubilized synaptic components and recombinant ovine prion protein (PrPrec) could be demonstrated by Biacore technology. Peroxynitrite abolished this interaction in a concentration‐dependent way and induced significant alterations of neuronal targets. Interaction was restored by prior addition of peroxynitrite trapping agents. Cu 2+ (in the form of CuSO 4 ) treatment of synaptosomes triggered a milder oxidative effect leading to a bell‐shaped increase of PrPrec binding to synaptosomal components, counteracted by the natural thiol agents, glutathione and thioredoxin. Copper(II)‐induced modifications of thiols in several neuronal proteins. A positive correlation was observed between PrPrec binding and immunoreactive changes for calcineurin B and its partners, suggesting a synergy between calcineurin complex and PrP for copper regulation.