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

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Russino D, McDonald E, Hejazi L, Hanson GR, Jones CE

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

ACS Chem Neurosci. 2013 Oct 16;4(10):1371-81. doi: 10.1021/cn4000988. Epub 2013 Aug 7.

PubMed ID

23875773 [ View in PubMed

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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 gamma 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 Cu(II) in an unusual [Cu(II)(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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Copper	Tachykinin-3	Protein	Humans	Unknown	Not Available	Details