Jump to main content
Jump to site search


NPY binds with heme to form a NPY-heme complex: enhances free heme’s peroxidase and promotes NPY nitration and inactivation

Abstract

Neuropeptide Y (NPY) is a member of the pancreatic peptide family of neuropeptides that play a crucial role in numerous central and peripheral nervous system responses. Recently, it has been shown that NPY protected cells against neurotoxic damage from β-amyloid peptides (Aβ) in Alzheimer's disease (AD). Heme is a common factor linking several metabolic perturbations in AD and altered heme metabolism has been shown a relationship to the pathologies of AD. Thus, heme may have a chance to meet NPY and potentially counteract its function. To explore this, UV-Visible spectroscopy, fluorescence spectroscopy and differential pulse voltammetry (DPV) were used to demonstrate that NPY can bind with heme to form a NPY-heme complex and the binding enhances the peroxidase activity of heme. Dot blotting result indicates that NPY is easily to be nitrated by binding with heme when H2O2 and NO2- are present. Furthermore, LC-MS/MS results confirm that tyrosine36 (Y36), an important amino acid residue of NPY in binding and activating for neuropeptide receptors, can be nitrated during the nitration process. Thereafter, we used mutant peptide NPY(3N)with Y36 replaced by 3-nitrtotyrosine to investigate the impact of nitration on the structure and bioactive of the peptide. Our results show that Y36 nitration destabilizes the α-helix conformation of the peptide, and counteract NPY-induced inhibition of cAMP accumulation in SK-N-MC cells. Collectively, these data imply that the self-association of NPY with heme potentially induces tyrosine nitration, destroys active monomeric conformation of the peptide and thereby counteracts its bioactivity

Back to tab navigation

Publication details

The article was received on 19 May 2017, accepted on 06 Jul 2017 and first published on 10 Jul 2017


Article type: Paper
DOI: 10.1039/C7DT01822C
Citation: Dalton Trans., 2017, Accepted Manuscript
  •   Request permissions

    NPY binds with heme to form a NPY-heme complex: enhances free heme’s peroxidase and promotes NPY nitration and inactivation

    H. Ye, Z. Yang, H. Li and Z. Gao, Dalton Trans., 2017, Accepted Manuscript , DOI: 10.1039/C7DT01822C

Search articles by author

Spotlight

Advertisements