Faculty Collaboration Database

Thiolate-based dinitrosyl iron complexes: Decomposition and detection and differentiation from S-nitrosothiols. Nitric Oxide 2017 May 01;65:1-9

Date

01/24/2017

Pubmed ID

28111306

Pubmed Central ID

PMC5663227

DOI

10.1016/j.niox.2017.01.007

Scopus ID

2-s2.0-85013354706 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

Dinitrosyl iron complexes (DNIC) spontaneously form in aqueous solutions of Fe(II), nitric oxide (NO), and various anions. They exist as an equilibrium between diamagnetic, dimeric (bi-DNIC) and paramagnetic, monomeric (mono-DNIC) forms. Thiolate groups (e.g., on glutathione or protein cysteine residues) are the most biologically relevant anions to coordinate to Fe(II). Low molecular weight DNIC have previously been suggested to be important mediators of NO biology in cells, and emerging literature supports their role in the control of iron-dependent cellular processes. Recently, it was shown that DNIC may be one of the most abundant NO-derived products in cells and may serve as intermediates in the cellular formation of S-nitrosothiols. In this work, we examined the stability of low molecular weight DNIC and investigated issues with their detection in the presence of other NO-dependent metabolites such as S-nitrosothiols. By using spectrophotometric, Electron Paramagnetic Resonance, ozone-based chemiluminesence, and HPLC techniques we established that at neutral pH, bi-DNIC remain stable for hours, whereas excess thiol results in decomposition to form nitrite. NO was also detected during the decomposition, but no S-nitrosothiol formation was observed. Importantly, mercury chloride accelerated the degradation of DNIC; thus, the implications of this finding for the diagnostic use of mercury chloride in the detection of S-nitrosothiols were determined in simple and complex biological systems. We conclude S-nitrosothiol levels may have been substantially overestimated in all methods where mercury chloride has been used.

Author List

Keszler A, Diers AR, Ding Z, Hogg N

Authors

Neil Hogg PhD Sr Associate Dean, Professor in the Biophysics department at Medical College of Wisconsin
Agnes Keszler PhD Research Scientist I in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cysteine
Ferrous Compounds
Glutathione
Humans
Hydrogen-Ion Concentration
Lipopolysaccharides
Luminescence
MCF-7 Cells
Mice
Nitric Oxide
Nitrites
RAW 264.7 Cells
S-Nitrosothiols
Spermine