Object's details: Ni(II) ions cleave and inactivate human alpha-1 antitrypsin hydrolytically, implicating nickel exposure as a contributing factor in pathologies related to antitrypsin deficiency

Provider:Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

Description

Title:
Ni(II) ions cleave and inactivate human alpha-1 antitrypsin hydrolytically, implicating nickel exposure as a contributing factor in pathologies related to antitrypsin deficiency
Creator:
Wezynfeld, Nina Ewa;
Bonna, Arkadiusz;
Bal, Wojciech;
Frączyk, Tomasz
Description:
Human alpha-1 antitrypsin (AAT) is an abundant serum protein, present at a concentration of 1.0–1.5 g x L−1. AAT deficiency is a genetic disease, manifesting itself with emphysema and liver cirrhosis, due to 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 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.
Object availability:
free access
Date:
2015
Type:
Article;
PeerReviewed
Publisher:
Royal Society of Chemistry
Relation: http://eprints.ibb.waw.pl/875 ;http://pubs.rsc.org/en/content/articlelanding/2014/mt/c4mt00316k#!divAbstract
Subject:
Q Science (General);
QD Chemistry;
QH301 Biology;
QP Physiology;
RB Pathology
Identifier:
Wezynfeld, Nina Ewa and Bonna, Arkadiusz and Bal, Wojciech and Frączyk, Tomasz (2015) Ni(II) ions cleave and inactivate human alpha-1 antitrypsin hydrolytically, implicating nickel exposure as a contributing factor in pathologies related to antitrypsin deficiency. Metallomics, 7 (4). pp. 596-604. ISSN 1756-591X
Data provider:
Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

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Object's details: Ni(II) ions cleave and inactivate human alpha-1 antitrypsin hydrolytically, implicating nickel exposure as a contributing factor in pathologies related to antitrypsin deficiency

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