NR APRK
AU Morot-Gaudry-Talarmain,Y.; Rezaei,H.; Guermonprez,L.; Treguer,E.; Grosclaude,J.
TI 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
QU Journal of Neurochemistry 2003 Dec; 87(6): 1456-70
PT journal article
AB 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 (PrPc) may play a neuroprotective function in participating in the redox control of neuronal environment and regulation of copper metabolism, a role impaired when PrPc is transformed into PrPsc in prion pathologies. The complex cross-talk between PrPc and cholinergic neurons was analyzed in vitro using peroxynitrite and Cu2+ 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. Cu2+ (in the form of CuSO4) 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.
MH Animals; Blotting, Western/methods; Calcineurin/*metabolism; Carbocyanines/metabolism; Choline O-Acetyltransferase/metabolism; Comparative Study; Copper Sulfate/*pharmacology; Cyclophilin A/metabolism; Cysteine/*analogs & derivatives/metabolism; Dose-Response Relationship, Drug; Epitopes/chemistry/immunology; Human; In Vitro; Membrane Glycoproteins/metabolism; Membrane Proteins/metabolism; Mercaptoethanol/pharmacology; Nerve Tissue Proteins/metabolism; Neurons/cytology/drug effects; Nitrosation/drug effects; Oxidation-Reduction/drug effects; Peroxynitrous Acid/*pharmacology; Prions/chemistry/*pharmacology; Protein Binding; Pyruvic Acid/pharmacology; Recombinant Proteins/metabolism; S-Nitrosothiols/metabolism; Sheep; Support, Non-U.S. Gov't; Synapsins/metabolism; Synaptic Vesicles/drug effects; Synaptosomes/*drug effects/metabolism; Tacrolimus Binding Proteins/metabolism; Thioredoxin/*metabolism; Time Factors; Torpedo; Tyrosine/*analogs & derivatives/metabolism; Tyrosine 3-Monooxygenase/metabolism
AD Laboratoire de Neurobiologie Cellulaire et Moleculaire, CNRS, Gif-sur-Yvette, France. morot@nbcm.cnrs-gif.fr
SP englisch
PO England