File(s) under permanent embargo
Glutaredoxin1 protects neuronal cells from copper-induced toxicity
journal contribution
posted on 2014-08-01, 00:00 authored by Michael Cater, Stephanie Materia, Z Xiao, K Wolyniec, S M Ackland, Yann Yap, Steve Cheung, Sharon La FontaineSharon La FontaineGlutaredoxin1 (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.
History
Journal
BiometalsVolume
27Issue
4Pagination
661 - 672Publisher
SpringerLocation
New York, N.Y.Publisher DOI
eISSN
1572-8773Language
engPublication classification
C Journal article; C1 Refereed article in a scholarly journalCopyright notice
2014, SpringerUsage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC