Effect of nitric oxide on the ligand-binding activity of albumin.
The redox state of the Cys-34 on albumin plays an important role in ligand binding of this plasma protein. We previously reported that mixed-disulfide formation of albumin with low molecular weight thiols, such as cysteine and glutathione, increased the affinity of this protein for phenolsulfophthalein (PSP) and Cu(II). Although nitric oxide (NO) and its metabolites easily react with various thiols, including that of albumin, and form S-nitrosothiol derivatives, the effect of such modification on the ligand-binding activity of this plasma protein remains to be elucidated. Kinetic analysis revealed that S-nitrosylation of Cys-34 on bovine serum albumin (BSA) decreased its binding activity for PSP. NO also decreased the ligand-binding activity of fresh plasma samples from rat and human. S-nitrosylation also decreased the binding activity of BSA for Cu(II). These results indicate that reversible modification of the Cys-34 by NO and oxidative stress might play regulatory roles in the binding and transport of organic anions and heavy metals in the circulation.
Kashiba-Iwatsuki
M
M
Department of Biochemistry, Osaka City University Medical School, Osaka, Japan.
Miyamoto
M
M
Inoue
M
M
D000818:Animals; D001769:Blood / Q000378:metabolism; D002417:Cattle; D003300:Copper / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D008024:Ligands; D009569:Nitric Oxide / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010637:Phenolsulfonphthalein / Q000378:metabolism; D051381:Rats; D012709:Serum Albumin / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000187:drug effects / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry
D004220:Disulfides; D008024:Ligands; D012709:Serum Albumin; D013438:Sulfhydryl Compounds; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; D003300:Copper; D010637:Phenolsulfonphthalein; D003545:Cysteine