Physical and functional interactions of cyclophilin B with neuronal actin and peroxiredoxin-1 are modified by oxidative stress

Presynaptic actin was identified as a new Torpedo cyclophilin B partner captured in pull-down experiments and by coimmunoprecipitation. The cyclophilin B–actin pull-down interaction was insensitive to the blockade of peptidyl cis/trans prolyl isomerase and calcineurin activities and to the latrunculin A- and jasplakinolide-mediated perturbation of F-actin polymerization. Conversely, it was reduced by ATP and stimulated by a low Cu2+ treatment of synaptosomes and by acrolydan-conjugated cyclophilin B. This Cu2+-induced stress, in parallel, stimulates the formation of GSH adducts with cysteines of synaptosomal actin followed by its deglutathionylation and its dimerization in the presence of higher Cu2+ concentrations. The reversibility of the thiol processing of actin occurred in the same range of Cu2+ concentrations that mediated a stronger cyclophilin B–actin interaction, suggesting cyclophilin B participation in antioxidant processes. Among 2-Cys-peroxiredoxin isoforms, mainly peroxiredoxin-1 was found in cell bodies and nerve endings. Functionally, both Torpedo and human peroxiredoxin-1 were activated in vitro by Torpedo cyclophilin B. Moreover, cyclophilin B, like thioredoxins, maintained an H2O2-dependent peroxidase activity of peroxiredoxin-1 in the presence of dithiothreitol. Thus, the monocysteinic Torpedo cyclophilin B is able to sustain peroxiredoxin-1 activity and might be involved in the presynaptic defense against oxidative stress affecting G-actin posttranslational changes and its redox signaling in nerve ending compartments.