Copper-dependent formation of disulfide-linked dimer of S100B protein.
Previous cell biological studies demonstrated that S100B protein enhances neurite extension of cortical neurons and stimulates proliferation of glial cells. Although these activities of the protein are ascribed to its disulfide-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 by copper-dependent oxidation of noncovalent S100B dimer. The disulfide-linked dimer markedly stimulated nitric oxide production in a microglial cell line, 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 signaling pathways.
Matsui Lee
I S
IS
Department of Biochemistry, Wakayama Medical College, Wakayama, 641-0012, Japan.
Suzuki
M
M
Hayashi
N
N
Hu
J
J
Van Eldik
L J
LJ
Titani
K
K
Nishikimi
M
M
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001324:Autoantigens / Q000737:chemistry / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D003300:Copper / Q000494:pharmacology*; D019281:Dimerization; D004220:Disulfides; D007700:Kinetics; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000502:physiology*; D009414:Nerve Growth Factors / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins
D001324:Autoantigens; D002135:Calcium-Binding Proteins; D004220:Disulfides; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579159:S100b protein, mouse; D003300:Copper; D001205:Ascorbic Acid; C029892:cupric chloride