Albumin fusion of thioredoxin - The production and evaluation of its biological activity for potential therapeutic applications

被引:41
作者
Ikuta, Shotaro [1 ]
Chuang, Victor Tuan Giam [1 ,2 ,3 ]
Ishima, Yu [1 ]
Nakajou, Keisuke [1 ]
Furukawa, Masato [1 ]
Watanabe, Hiroshi [1 ]
Maruyama, Toru [1 ]
Otagiri, Masaki [1 ,2 ]
机构
[1] Kumamoto Univ, Grad Sch Pharmaceut Sci, Dept Biopharmaceut, Kumamoto 8620973, Japan
[2] Sojo Univ, Fac Pharmaceut Sci, Kumamoto, Japan
[3] Curtin Univ Technol, Curtin Hlth Innovat Res Inst, Sch Pharm, Perth, WA, Australia
关键词
Human serum albumin; Recombinant albumin; Thioredoxin; Fusion protein; Endotoxic shock; Pharmacokinetic; Pharmacodynamic; HUMAN SERUM-ALBUMIN; CHRONIC HEPATITIS-C; PICHIA-PASTORIS; S-NITROSYLATION; IN-VITRO; PROTEIN; MICE; PHARMACOKINETICS; CHEMOTAXIS; ISCHEMIA;
D O I
10.1016/j.jconrel.2010.05.020
中图分类号
O6 [化学];
学科分类号
070301 [无机化学];
摘要
Thioredoxin-1 (Trx) is a redox-active protein with anti-inflammatory effects. The effect of albumin fusion on the pharmacokinetic and pharmacodynamic properties of Trx was evaluated in this study. The findings indicate that the properties of human serum albumin and the fusion protein are comparable. The fusion protein showed similar plasma concentration and organ distribution profiles as human serum albumin. The fusion protein accumulated in lungs, reaching levels higher than Trx. In an insulin reducing assay, the activity of the fusion protein was 60% of the activity of Trx. However, survival rate of endotoxic shock mice induced by the administration of a lipopolysaccharide and D-galactosamine for fusion protein was double that of Trx. The findings reported herein indicate that the fusion protein is likely to have great clinical applications in areas such as the treatment of reperfusion injuries. Crown Copyright (C) 2010 Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:17 / 23
页数:7
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