NDLI: Coordination-triggered NO release from a dinitrosyl iron complex leads to anti-inflammatory activity

Content Provider	Royal Society of Chemistry (RSC)
Author	Chung, Su Wol Kwon, Min-Young Skodje, Kelsey M. Kim, Eunsuk
Copyright Year	2014
Abstract	Dinitrosyl iron complexes (DNICs) are widely considered NO storage and donor molecules in cells. However, what induces an NO release from iron in DNICs and the subsequent biological consequences remain elusive. The chemistry and biology of the NO release activity of DNICs are reported here. Changes in redox status or coordination number of discrete N-bound DNICs, respectively [Fe(TMEDA)(NO)2] (1) and [Fe(TMEDA)(NO)2I] (2), can generate a metastable {Fe(NO)2}9 DNIC, [Fe(TMEDA)(NO)2]+, with νNO at 1769 and 1835 cm−1 and an EPR signal at g = 2.04, that spontaneously releases NO in solution. The NO release activity of 2 results in the up- and downregulation of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS), respectively, in murine RAW 264.7 macrophages. Furthermore, treatment with 2 leads to downregulation of pro-inflammatory cytokines, TNF-α and IL-6, and upregulation of the anti-inflammatory cytokine, IL-10. Taken together, these results demonstrate that the appropriate control of redox and coordination chemistry of DNICs could enable them to become anti-inflammatory agents, suggesting a potential new role for cellular DNICs.
Starting Page	2374
Ending Page	2378
Page Count	5
File Format	HTM / HTML PDF
ISSN	20416520
Volume Number	5
Issue Number	6
Journal	Chemical Science
DOI	10.1039/c3sc53319k
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Coordination number EPR Heme oxygenase Cytokine Redox Coordination complex Metastability Interleukin 6 Chemistry Tumor necrosis factor alpha Interleukin 10 HMOX1 Nitric oxide synthase Raw image format Tetramethylethylenediamine Molecular biology Macrophage
Content Type	Text
Resource Type	Article
Subject	Chemistry

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