Format

Send to

Choose Destination
See comment in PubMed Commons below
Free Radic Biol Med. 2011 Oct 15;51(8):1558-66. doi: 10.1016/j.freeradbiomed.2011.06.030. Epub 2011 Jul 5.

Dinitrosyliron complexes are the most abundant nitric oxide-derived cellular adduct: biological parameters of assembly and disappearance.

Author information

  • 1Department of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.

Abstract

It is well established that nitric oxide ((•)NO) reacts with cellular iron and thiols to form dinitrosyliron complexes (DNIC). Little is known, however, regarding their formation and biological fate. Our quantitative measurements reveal that cellular concentrations of DNIC are proportionally the largest of all (•)NO-derived adducts (900 pmol/mg protein, or 45-90 μM). Using murine macrophages (RAW 264.7), we measured the amounts, and kinetics, of DNIC assembly and disappearance from endogenous and exogenous sources of (•)NO in relation to iron and O(2) concentration. Amounts of DNIC were equal to or greater than measured amounts of chelatable iron and depended on the dose and duration of (•)NO exposure. DNIC formation paralleled the upregulation of iNOS and occurred at low physiologic (•)NO concentrations (50-500 nM). Decreasing the O(2) concentration reduced the rate of enzymatic (•)NO synthesis without affecting the amount of DNIC formed. Temporal measurements revealed that DNIC disappeared in an oxygen-independent manner (t(1/2)=80 min) and remained detectable long after the (•)NO source was removed (>24 h). These results demonstrate that DNIC will be formed under all cellular settings of (•)NO production and that the contribution of DNIC to the multitude of observed effects of (•)NO must always be considered.

Copyright © 2011 Elsevier Inc. All rights reserved.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk