TY - JOUR
T1 - One-step preparation of S-nitrosated human serum albumin with high biological activities
AU - Ishima, Yu
AU - Hiroyama, Shuichi
AU - Kragh-Hansen, Ulrich
AU - Maruyama, Toru
AU - Sawa, Tomohiro
AU - Akaike, Takaaki
AU - Kai, Toshiya
AU - Otagiri, Masaki
N1 - Funding Information:
This work was supported in part by Grants-in-Aid from the Japan Society for the Promotion of Science (JSPS) , a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan ( 18390051 ), and by Fonden af 1870 . Thanks are also due to members of the Gene Technology Center in Kumamoto University for their important contributions to the experiments.
PY - 2010/9
Y1 - 2010/9
N2 - S-Nitrosated human serum albumin (SNO-HSA) is a large molecular weight nitric oxide carrier in human plasma, and because of its many beneficial effects in different tests, it is currently under investigation as a cytoprotective agent. However, making SNO-HSA preparations is a complicated and time-consuming process. We found that binding of caprylic acid (CA) and N-acetyl-l-tryptophan (N-AcTrp) to defatted mercaptalbumin increased S-nitrosation by S-nitrosoglutathione (GS-NO) by making Cys-34 of HSA more accessible and by protecting it against oxidation, respectively. Fortunately, HSA solutions for clinical use contain high concentrations of CA and N-AcTrp as stabilizers. By making use of that fact it was possible to work-out a fast and simple procedure for producing SNO-HSA: incubation of a commercial HSA formulation with GS-NO for only 1. min results in S-nitrosation of HSA. The biological usefulness of such a preparation was tested in a rat ischemia-reperfusion liver injury model. Although our procedure for making SNO-HSA is fast and straightforward, the cytoprotective effect of the preparation was similar to, or better than, that of a preparation made in a more traditional way. The clinical development of SNO-HSA as a strong cytoprotective agent is under way using this method in collaboration with clinicians and industrial developers.
AB - S-Nitrosated human serum albumin (SNO-HSA) is a large molecular weight nitric oxide carrier in human plasma, and because of its many beneficial effects in different tests, it is currently under investigation as a cytoprotective agent. However, making SNO-HSA preparations is a complicated and time-consuming process. We found that binding of caprylic acid (CA) and N-acetyl-l-tryptophan (N-AcTrp) to defatted mercaptalbumin increased S-nitrosation by S-nitrosoglutathione (GS-NO) by making Cys-34 of HSA more accessible and by protecting it against oxidation, respectively. Fortunately, HSA solutions for clinical use contain high concentrations of CA and N-AcTrp as stabilizers. By making use of that fact it was possible to work-out a fast and simple procedure for producing SNO-HSA: incubation of a commercial HSA formulation with GS-NO for only 1. min results in S-nitrosation of HSA. The biological usefulness of such a preparation was tested in a rat ischemia-reperfusion liver injury model. Although our procedure for making SNO-HSA is fast and straightforward, the cytoprotective effect of the preparation was similar to, or better than, that of a preparation made in a more traditional way. The clinical development of SNO-HSA as a strong cytoprotective agent is under way using this method in collaboration with clinicians and industrial developers.
KW - Caprylic acid
KW - Human serum albumin
KW - Ischemia-reperfusion
KW - N-Acetyl-l-tryptophan
KW - Nitric oxide
KW - S-Nitrosation
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U2 - 10.1016/j.niox.2010.05.002
DO - 10.1016/j.niox.2010.05.002
M3 - Article
C2 - 20451647
AN - SCOPUS:77954620591
SN - 1089-8603
VL - 23
SP - 121
EP - 127
JO - Nitric Oxide - Biology and Chemistry
JF - Nitric Oxide - Biology and Chemistry
IS - 2
ER -
