Peptide bond cleavage in the presence of Ni-containing particles.

NiO nanoparticles and non-stoichiometric black NiO were shown to be effective sources of Ni2+ ions causing sequence-selective peptide bond hydrolysis. NiO nanoparticles were as effective in this reaction as their molar equivalent of soluble Ni(ii) salt. These findings highlight the efficacy of delivery of toxic Ni2+ by these environmentally available particles.

Cu transfer from amyloid-ß4-16 to metallothionein-3: the role of the neurotransmitter glutamate and metallothionein-3 Zn(ii)-load states.

Copper transfer from Cu(ii)amyloid-ß4-16 to human Zn7-metallothionein-3 can be accelerated by glutamate and by lowering the Zn-load of metallothionein-3 with EDTA. Glutamate facilitates the Cu(ii) release, and Zn4-6-metallothionein-3 react more rapidly. These mechanisms are additive, proving the intricate and interconnected network of zinc and copper trafficking between biomolecules.

Ni(ii) ions cleave and inactivate human alpha-1 antitrypsin hydrolytically, implicating nickel exposure as a contributing factor in pathologies related to antitrypsin deficiency.

Human alpha-1 antitrypsin (AAT) is an abundant serum protein present at a concentration of 1.0-1.5 g L(-1). AAT deficiency is a genetic disease that manifests with emphysema and liver cirrhosis due to the accumulation of a misfolded AAT mutant in hepatocytes. Lung AAT amount is inversely correlated with chronic obstructive pulmonary disease (COPD), a serious and often deadly condition, with increasing frequency in the aging population. Exposure to cigarette smoke and products of fossil fuel combustion aggravates AAT deficiency and COPD according to mechanisms that are not fully understood. Taking into account that these fumes contain particles that can release nickel to human airways and skin, we decided to investigate interactions of AAT with Ni(ii) ions within the paradigm of Ni(ii)-dependent peptide bond hydrolysis. We studied AAT protein derived from human blood using HPLC, SDS-PAGE, and mass spectrometry. These studies were aided by spectroscopic experiments on model peptides. As a result, we identified three hydrolysis sites in AAT. Two of them are present in the N-terminal part of the molecule next to each other (before Thr-13 and Ser-14 residues) and effectively form one N-terminal cleavage site. The single C-terminal cleavage site is located before Ser-285. The N-terminal hydrolysis was more efficient than the C-terminal one, but both abolished the ability of AAT to inhibit trypsin in an additive manner. Nickel ions bound to hydrolysis products demonstrated an ability to generate ROS. These results implicate Ni(ii) exposure as a contributing factor in AAT-related pathologies.

cis-Urocanic acid as a potential nickel(II) binding molecule in the human skin.

cis-Urocanic acid, a derivative of histidine, is one of the essential components of human skin. We found that it can bind nickel(II) ions in a pH-dependent manner, with the dissociation constant in the low millimolar range, as revealed by potentiometry, and confirmed by isothermal titration calorimetry and UV-vis spectroscopy. The binding occurs within the physiological skin pH range. Considering the fact that cis-urocanic acid is present in the human skin in concentrations as high as millimolar, this molecule may be a physiologically important player in nickel trafficking in the human organism.