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

Jason R. Hickok, Sumit Sahni, Hong Shen, Akanksha Arvind, Chloe Antoniou, Leslie W M Fung, Douglas D. Thomas

Research output: Contribution to journalArticle

89 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1558-1566
Number of pages9
JournalFree Radical Biology and Medicine
Volume51
Issue number8
DOIs
Publication statusPublished - 15 Oct 2011

Keywords

  • Chelatable iron pool
  • Dinitrosyliron complexes
  • Free radicals
  • Nitric oxide
  • S-nitrosothiols

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