Glutaredoxin1 protects neuronal cells from copper-induced toxicity

Cater, Michael A., Materia, Stephanie, Xiao, Zhiguang, Wolyniec, Kamil, Ackland, Susan M., Yap,Yann W., Cheung, Nam Sang and La Fontaine, Sharon 2014, Glutaredoxin1 protects neuronal cells from copper-induced toxicity, Biometals, vol. 27, no. 4, pp. 661-672, doi: 10.1007/s10534-014-9748-1.

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Title Glutaredoxin1 protects neuronal cells from copper-induced toxicity
Author(s) Cater, Michael A.
Materia, Stephanie
Xiao, Zhiguang
Wolyniec, Kamil
Ackland, Susan M.
Yap,Yann W.
Cheung, Nam SangORCID iD for Cheung, Nam Sang
La Fontaine, SharonORCID iD for La Fontaine, Sharon
Journal name Biometals
Volume number 27
Issue number 4
Start page 661
End page 672
Total pages 12
Publisher Springer
Place of publication New York, N.Y.
Publication date 2014-08
ISSN 1572-8773
Keyword(s) copper
oxidative stress
Thiol oxidoreductase
Summary Glutaredoxin1 (GRX1) is a glutathione (GSH)-dependent thiol oxidoreductase. The GRX1/GSH system is important for the protection of proteins from oxidative damage and in the regulation of protein function. Previously we demonstrated that GRX1/GSH regulates the activity of the essential copper-transporting P1B-Type ATPases (ATP7A, ATP7B) in a copper-responsive manner. It has also been established that GRX1 binds copper with high affinity and regulates the redox chemistry of the metallochaperone ATOX1, which delivers copper to the copper-ATPases. In this study, to further define the role of GRX1 in copper homeostasis, we examined the effects of manipulating GRX1 expression on copper homeostasis and cell survival in mouse embryonic fibroblasts and in human neuroblastoma cells (SH-SY5Y). GRX1 knockout led to cellular copper retention (especially when cultured with elevated copper) and reduced copper tolerance, while in GRX1-overexpressing cells challenged with elevated copper, there was a reduction in both intracellular copper levels and copper-induced reactive oxygen species, coupled with enhanced cell proliferation. These effects are consistent with a role for GRX1 in regulating ATP7A-mediated copper export, and further support a new function for GRX1 in neuronal copper homeostasis and in protection from copper-mediated oxidative injury.
Language eng
DOI 10.1007/s10534-014-9748-1
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2014, Springer
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