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Human serum albumin-thioredoxin fusion protein with long blood retention property is effective in suppressing lung injury.
MedLine Citation:
PMID:  21620911     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Thioredoxin (Trx) is a redox-active protein with anti-inflammatory effects but with a short half life of 1h. Genetic fusion of Trx to human serum albumin (HSA) extended its half life without causing significant loss of its biological activities. HSA-Trx caused a decrease in the number of cells in brochoalveolar lavage fluid, the wet/dry ratio and the inflammation at the respiratory tract of the ovalbumin (OVA) induced lung injury model mouse. Three intraperitoneal doses of Trx alone produced the same extent of suppression of those three detrimental effects of OVA as one intravenous dose of HSA-Trx. Inhibition experiments confirmed that reactive oxygen species (ROS) and reactive nitrogen species (RNS) involved in the progression of the injury. HSA-Trx inhibited the production of ROS as confirmed in the EPR experiment, but lung tissue staining suggested that induced nitrogen oxide synthase (iNOS) was not suppressed by the fusion protein. Instead, the production of nitrotyrosine, 8-nitro-cGMP, and 8-hydroxy-2'-deoxyguanosine downstream to the iNOS has been inhibited. This suggested that HSA-Trx produced lung protection effect via different mechanisms from Trx alone. HSA-Trx retains the biological properties of Trx thus has great potential in treating oxidative stress related diseases.
Authors:
Masato Furukawa; Ryota Tanaka; Victor Tuan Giam Chuang; Yu Ishima; Kazuaki Taguchi; Hiroshi Watanabe; Toru Maruyama; Masaki Otagiri
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-17
Journal Detail:
Title:  Journal of controlled release : official journal of the Controlled Release Society     Volume:  -     ISSN:  1873-4995     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier B.V.
Affiliation:
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto-shi, Kumamoto 862-0973, Japan.
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