posted on 2013-10-16, 00:00authored byDebora Russino, Elle McDonald, Leila Hejazi, Graeme R. Hanson, Christopher E. Jones
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.