Copper-dependent formation of disulfide-linked dimer of S100B protein

Previous cell biological studies demonstrated that S100B protein enhances n eurite extension of cortical neurons and stimulates proliferation of glial cells. Although these activities of the protein are ascribed to its disulfi de-linked dimeric form, there have been no indications as to how the dimer is formed in vivo. We have found by an in vitro study that it is produced b y copper-dependent oxidation of noncovalent S100B dimer, The disulfide-link ed dimer markedly stimulated nitric oxide production in a microglial cell l ine, BV2, Interestingly, the disulfide-linked dimer formation was found to be prevented by ascorbic acid. The copper-dependent formation of the dimer may not happen in vivo under normal conditions; however, under pathological conditions where copper is likely to be released from tissues and catalyze autoxidation of ascorbic acid, the dimer formation may proceed, resulting in the stimulated production of nitric oxide that would induce toxic signal ing pathways. (C) 2000 Academic Press.