Effects of endogenous ligands on the biological role of human serum albumin in S-nitrosylation.
Many proteins have been identified as targets for S-nitrosylation, including structural and signaling proteins, a nd ion channels. S-nitrosylation plays an important role in regulating their activity and function. We used human serum albumin (HS A), a major endogenous NO traffic protein, and studied the effect of mediators on S-nitrosylation processes which control NO bioactivity. By using NOC-7, S-nitrosoglutathione, and activated RAW264.7 cells as NO-donors we found that high-affinity binding of endogenous ligands (Cu(2+), bilirubin and fatty acid) can affect these processes. It is likely that the same effects take place in many clinical situations characterized by increased fatty acid concentrations in plasma such as type II diabetes and the metabolic syndrome. Thus, endogenous ligands, changing their plasma concentrations, could be a novel type of mediator of S-nitrosylation not only in the case of HSA but also for other target proteins.
Ishima
Yu
Y
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 O e-honmachi, Kumamoto 862-0973, Japan.
Akaike
Takaaki
T
Kragh-Hansen
Ulrich
U
Hiroyama
Shuichi
S
Sawa
Tomohiro
T
Maruyama
Toru
T
Kai
Toshiya
T
Otagiri
Masaki
M
D000818:Animals; D002460:Cell Line; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009603:Nitroso Compounds / Q000737:chemistry*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism*
C115239:3-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-propanamine; D006834:Hydrazines; D008024:Ligands; D009603:Nitroso Compounds; D012709:Serum Albumin; C001702:mercaptoalbumin