The tachykinin peptide, neurokinin B, binds copper, forming an unusual [CuII(NKB)2] complex, and inhibits copper uptake into 1321N1 astrocytoma cells

Russino, Debora, McDonald, Elle, Hejazi, Leila, Hanson, Graeme R. and Jones, Christopher E. (2013) The tachykinin peptide, neurokinin B, binds copper, forming an unusual [CuII(NKB)2] complex, and inhibits copper uptake into 1321N1 astrocytoma cells. ACS Chemical Neuroscience, 4 10: 1371-1381. doi:10.1021/cn4000988

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Author Russino, Debora
McDonald, Elle
Hejazi, Leila
Hanson, Graeme R.
Jones, Christopher E.
Title The tachykinin peptide, neurokinin B, binds copper, forming an unusual [CuII(NKB)2] complex, and inhibits copper uptake into 1321N1 astrocytoma cells
Formatted title
The tachykinin peptide, neurokinin B, binds copper, forming an unusual [CuII(NKB)2] complex, and inhibits copper uptake into 1321N1 astrocytoma cells
Journal name ACS Chemical Neuroscience   Check publisher's open access policy
ISSN 1948-7193
Publication date 2013-07-22
Year available 2013
Sub-type Article (original research)
DOI 10.1021/cn4000988
Open Access Status DOI
Volume 4
Issue 10
Start page 1371
End page 1381
Total pages 11
Place of publication Washington, DC, United States
Publisher American Chemical Society
Collection year 2014
Language eng
Formatted abstract
Neurokinin B (NKB) is a member of the tachykinin family of neuropeptides that have neuroinflammatory, neuroimmunological, and neuroprotective functions. In a neuroprotective role, tachykinins can help protect cells against the neurotoxic processes observed in Alzheimer’s disease. A change in copper homeostasis is a clear feature of Alzheimer’s disease, and the dysregulation may be a contributory factor in toxicity. Copper has recently been shown to interact with neurokinin A and neuropeptide γ and can lead to generation of reactive oxygen species and peptide degradation, which suggests that copper may have a place in tachykinin function and potentially misfunction. To explore this, we have utilized a range of spectroscopic techniques to show that NKB, but not substance P, can bind CuII in an unusual [CuII(NKB)2] neutral complex that utilizes two N-terminal amine and two imidazole nitrogen ligands (from each molecule of NKB) and the binding substantially alters the structure of the peptide. Using 1321N1 astrocytoma cells, we show that copper can enter the cells and subsequently open plasma membrane calcium channels but when bound to neurokinin B copper ion uptake is inhibited. This data suggests a novel role for neurokinin B in protecting cells against copper-induced calcium changes and implicates the peptide in synaptic copper homeostasis.
Keyword Neurokinin B
Tachykinin
Copper
Calcium
Neurodegeneration
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Centre for Advanced Imaging Publications
 
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Created: Tue, 23 Jul 2013, 16:47:45 EST by Sandrine Ducrot on behalf of Centre for Advanced Imaging