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dc.contributor.authorTanaka, K.
dc.contributor.authorShimoda, M.
dc.contributor.authorChuang, Victor
dc.contributor.authorNishida, K.
dc.contributor.authorKawahara, M.
dc.contributor.authorIshida, T.
dc.contributor.authorOtagiri, M.
dc.contributor.authorMaruyama, T.
dc.contributor.authorIshima, Y.
dc.date.accessioned2017-11-24T05:24:53Z
dc.date.available2017-11-24T05:24:53Z
dc.date.created2017-11-24T04:48:44Z
dc.date.issued2018
dc.identifier.citationTanaka, K. and Shimoda, M. and Chuang, V. and Nishida, K. and Kawahara, M. and Ishida, T. and Otagiri, M. et al. 2018. Thioredoxin-albumin fusion protein prevents copper enhanced zinc-induced neurotoxicity via its antioxidative activity. International Journal of Pharmaceutics. 535 (1-2): pp. 140-147.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/58282
dc.identifier.doi10.1016/j.ijpharm.2017.11.012
dc.description.abstract

© 2017 Elsevier B.V. Zinc (Zn) is a co-factor for a vast number of enzymes, and functions as a regulator for immune mechanism and protein synthesis. However, excessive Zn release induced in pathological situations such as stroke or transient global ischemia is toxic. Previously, we demonstrated that the interaction of Zn and copper (Cu) is involved in the pathogenesis of Alzheimer's disease and vascular dementia. Furthermore, oxidative stress has been shown to play a significant role in the pathogenesis of various metal ions induced neuronal death. Thioredoxin-Albumin fusion (HSA-Trx) is a derivative of thioredoxin (Trx), an antioxidative protein, with improved plasma retention and stability of Trx. In this study, we examined the effect of HSA-Trx on Cu 2+ /Zn 2+ -induced neurotoxicity. Firstly, HSA-Trx was found to clearly suppress Cu 2+ /Zn 2+ -induced neuronal cell death in mouse hypothalamic neuronal cells (GT1-7 cells). Moreover, HSA-Trx markedly suppressed Cu 2+ /Zn 2+ -induced ROS production and the expression of oxidative stress related genes, such as heme oxygenase-1. In contrast, HSA-Trx did not affect the intracellular levels of both Cu 2+ and Zn 2+ after Cu 2+ /Zn 2+ treatment. Finally, HSA-Trx was found to significantly suppress endoplasmic reticulum (ER) stress response induced by Cu 2+ /Zn 2+ treatment in a dose dependent manner. These results suggest that HSA-Trx counteracted Cu 2+ /Zn 2+ -induced neurotoxicity by suppressing the production of ROS via interfering the related gene expressions, in addition to the highly possible radical scavenging activity of the fusion protein. Based on these findings, HSA-Trx has great potential as a promising therapeutic agent for the treatment of refractory neurological diseases.

dc.publisherElsevier BV
dc.titleThioredoxin-albumin fusion protein prevents copper enhanced zinc-induced neurotoxicity via its antioxidative activity
dc.typeJournal Article
dcterms.source.volume535
dcterms.source.number1-2
dcterms.source.startPage140
dcterms.source.endPage147
dcterms.source.issn0378-5173
dcterms.source.titleInternational Journal of Pharmaceutics
curtin.departmentSchool of Pharmacy
curtin.accessStatusFulltext not available


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