Regulation of neuronal cell functions by S-nitroso-cysteine

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Previously, we proposed a new signal transduction mechanism [NO radical-S-nitroso-thiols formation-S-nitrosylation of proteins]. In the present study, we obtained several new findings concerning the effects of S-nitroso-cysteine on neuronal cell functions. 1) InPC12 cells, an inhibitor of thioredoxin reductase (DNCB) caused apoptosis with caspase activation. Treatment with NO compounds including S-nitroso-cysteine inhibited the caspase activation and the apoptosis. 2) S-Nitroso-cysteine, but not other NO compounds, stimulated noradrenaline release from rat brain slices. S-Nitroso-cysteine acted as a sulfhydryl agent on proteins that regulate noradrenaline release. 3) Modification of the oxidation status of the sulfhydryl groups on the caffeine-sensitive receptors by S-nitroso-cysteine regulated Ca2+ channel activity in a reversible manner in PC12 cells. 4) S-Nitroso-cysteine regulated translocation of vesicles containing synaptophysin and SNAP-25 in PC12 cells. 5) S-Nitroso-cysteine reacted with cysteine residues in GTP-binding proteins such as Gi/Go, causing inhibition of ADP-ribosylation by pertussis toxin. 6) Arachidonic acid release from PC12 cells was inhibited by cytosolic phospholipase A2 inhibitors and by S-nitroso-cysteine, but not by other NO compounds. These findings show the regulation of neuronal cell functions by S-nitroso-cysteine.