Cited by 155Nitric Oxide and Endothelin EffectsHemoglobin structure and functionRedox biology and oxidative stress

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

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Hickok, Jason R., Sahni, Sumit, Shen, Hong, Arvind, Akanksha, Antoniou, Chloe, Fung, Leslie W.M., Thomas, Douglas D.·2011·Free Radical Biology and Medicine

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.

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Crossref · 10.1016/j.freeradbiomed.2011.06.030

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  • Excess NO reacts with the chelatable iron pool to quantitatively convert it to paramagnetic DNICs with thiol ligands.

    “Reaction of excess NO with the CIP leads to quantitative conversion to paramagnetic dinitrosyliron complexes (DNICs) with thiol containing ligands [250, 251].”

    From Signaling and stress: The redox landscape in NOS2 biology (2015) · cites this paper as [250]

  • Thomas et al. proposed that dinitrosyl-iron-complexes (DNICs) represent the most abundant NO-containing material in biological tissue.

    “Thomas et al. proposed these species to represent the most abundant NOcontaining material in biological tissue [102].”

    From On the chemical biology of the nitrite/sulfide interaction (2015) · cites this paper as [102]

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Authors
Hickok, J. R., Sahni, S., Shen, H., Arvind, A., Antoniou, C., Fung, L. W. M., & Thomas, D. D.
Affiliations
  • University of Illinois Chicago (US)
  • University of Chicago (US)
Corresponding author
Thomas, Douglas D.
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2011-10
Volume
51
Issue
8
Pages
1558-1566
ISSN
0891-5849 (ISSN-L)
OpenAlex
W2085719171
Cited by
155
References
34
Citations by year
2026: 5 · 2025: 6 · 2024: 9 · 2023: 10 · 2022: 6 · 2021: 16 · 2020: 11 · 2019: 13 · 2018: 13 · 2017: 12 · 2016: 14 · 2015: 7 · 2014: 14 · 2013: 9 · 2012: 8
FWCI
7.20
Type
journal article
Language
en
Open access
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (K22CA113315)
  • National Institute of General Medical Sciences (R01GM068621, R01GM094175)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
nitric oxide, iron, thiols, macrophages, inducible nitric oxide synthase, oxygen concentration
MeSH terms
Animals, Cell Line, Electron Spin Resonance Spectroscopy, Iron, Macrophages, Nitric Oxide, Nitrogen Oxides, Oxygen, Reactive Nitrogen Species, Mice

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