One-step preparation of S-nitrosated human serum albumin with high biological activities

Yu Ishima, Shuichi Hiroyama, Ulrich Kragh-Hansen, Toru Maruyama, Tomohiro Sawa, Takaaki Akaike, Toshiya Kai, Masaki Otagiri

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)121-127
Number of pages7
JournalNitric Oxide - Biology and Chemistry
Volume23
Issue number2
DOIs
Publication statusPublished - 2010 Sep
Externally publishedYes

Keywords

  • Caprylic acid
  • Human serum albumin
  • Ischemia-reperfusion
  • N-Acetyl-l-tryptophan
  • Nitric oxide
  • S-Nitrosation

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research

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