Disease relevance of dinitrosyl iron complex

• Such formed ferredoxin dinitrosyl iron complex is efficiently repaired in E. coli cells even in the absence of new protein synthesis [1].
• This report demonstrates that iron-nitrosyl EPR signals similar to those observed in macrophages and during sepsis are present in the blood and in the grafted tissue of rats during the rejection of allogeneic (but not syngeneic) heart grafts [2].
• Dinitrosyl iron complex (DNIC, 200 microg/kg, single dose, iv), a NO donor, decreases the resistance of animals to acute hypoxia by 30% [3].

High impact information on dinitrosyl iron complex

• In the third model, mitochondria lost preformed iron-nitrosyl complexes when exposed to blood [4].
• RESULTS: Iron-nitrosyl complexes and hepatocyte mitochondrial dysfunction were observed in the in vitro model and prevented by an NO synthase inhibitor [4].
• Here, we discuss some recent studies focusing on iron nutrition in plants as well as evidence from iron homeostasis in animals and propose a new scenario involving the formation of nitric oxide and iron-nitrosyl complexes as part of the dynamic network that governs plant iron homeostasis [5].
• EPR demonstration of iron-nitrosyl complex formation by cytotoxic activated macrophages [6].
• K562 cells did not produce any appreciable levels of NO, but they were targeted by RNIs released from the cytokine-stimulated vascular cells, as demonstrated by electron paramagnetic resonance spectrometry, which showed formation of nonheme iron-nitrosyl complexes in the tumor cells [7].

Chemical compound and disease context of dinitrosyl iron complex

• Here we show that cysteine desulfurase encoded by the gene iscS of E. coli can directly convert the ferredoxin dinitrosyl iron complex to the ferredoxin [2Fe-2S] cluster in the presence of L-cysteine in vitro [8].

Biological context of dinitrosyl iron complex

• Low oxygen tension did not affect S-nitrosation by the dinitrosyl-iron complex thus excluding the involvement of oxygenated NOx-species in the nitrosation reaction [9].
• Electron paramagnetic resonance (EPR) studies have shown the formation of iron-nitrosyl species during macrophage activation and also during sepsis, indicating that alteration of iron-containing protein function may be the result of the well-documented tendency of NO to bind to metal ions [2].
• Nitric oxide (NO) donors (S-nitrosoglutathione and dinitrosyl iron complex) reversibly inhibited activity of n-SMase and decreased level of lipid peroxidation products [10].
• It was shown that 2 hours after the administration of the NO donor dinitrosyl iron complex (DNIC), the gene expression of myocardial SERCA was increased by 20% as compared to the control [11].

Anatomical context of dinitrosyl iron complex

• Interleukin-1 beta-induced formation of EPR-detectable iron-nitrosyl complexes in islets of Langerhans. Role of nitric oxide in interleukin-1 beta-induced inhibition of insulin secretion [12].
• Coinduction of nitric oxide synthesis and intracellular nonheme iron-nitrosyl complexes in murine cytokine-treated fibroblasts [13].
• When porcine aortic endothelial or smooth muscle cells in culture were incubated under anaerobic conditions with SNP, an EPR spectrum was obtained, which could be resolved into the signal for penta and a signal previously described as a nonheme iron-nitrosyl-sulfur complex, Fe-NOSR [14].
• The origin of dinitrosyl-iron complex in endothelial cells [15].

Associations of dinitrosyl iron complex with other chemical compounds

• BACKGROUND & AIMS: Nitric oxide forms inactive iron-nitrosyl complexes within hepatic mitochondria in vitro [4].
• In the in vivo model, however, despite a 130-fold increase in plasma nitrate levels and formation of hemoglobin-NO complexes in blood, no iron-nitrosyl complex was detected in hepatic mitochondria, and hepatic mitochondrial function was not impaired [4].
• In search of such cellular factors, we find that l-cysteine can effectively eliminate the EPR signal of the ferredoxin dinitrosyl iron complex and release the ferrous iron from the complex [1].
• In the presence of excess reductant (sodium ascorbate), iron(II)-BFR also catalyses the reduction of NO to N2O, giving rise to three mononuclear iron-nitrosyl species which are detectable by EPR [16].
• The appearance of a less stable dinitrosyl-iron complex with phosphate was detected when solutions of iron(II)-citrate containing 100 mM phosphate buffer (pH 7.4) were mixed with S-nitrosocysteine or NO-proline [17].

Gene context of dinitrosyl iron complex

• Hepatocytes exposed to IFN-gamma, TNF-alpha, IL-1 beta, and LPS demonstrated the appearance of a g = 2.04 axial EPR signal indicative of the formation of nonheme iron-nitrosyl complexes [18].
• A key factor in the inhibitory effect of IL-1 beta and TNF in rat islets is the generation of nitric oxide which inactivates enzymes such as aconitase and ribonucleotide reductase by formation of iron-nitrosyl complexes [19].
• These findings suggest specifically N-nitrosation of glutathione reductase as a likely mechanism of inhibition elicited by dinitrosyl-iron complex and demonstrate in general that structural resemblance of an NO carrier with a natural ligand enhances NO+ transfer to the ligand-binding protein [20].
• The use of several spectroscopic tools such as EPR, ENDOR, FTIR, Mössbauer, and UV-visible spectroscopies as well as mass spectrometry analysis was necessary to characterize the iron-nitrosyl species in Fur [21].
• Earlier studies showed that the characterization of iron binding to BFR could be aided by EPR analysis of iron-nitrosyl species resulting from the addition of NO to the protein [Le Brun, Cheesman, Andrews, Harrison, Guest, Moore and Thomson (1993) FEBS Lett. 323, 261-266] [16].

Analytical, diagnostic and therapeutic context of dinitrosyl iron complex

• In contrast, in allografts on POD4, a new axial signal at g = 2.04 and g = 2.02 appeared that was attributed to the dinitrosyl-iron complex formed by nitrosylation of non-heme protein [22].
• A novel cyclic tetra-nuclear dinitrosyl iron complex [Fe(NO)2(Im-H)]4 was isolated and characterized by X-ray crystallography, and in donor solvents this fragments into 17 e- monomeric units that give EPR spectra analogous to the g= 2.03 species seen in mammalian biology [23].
• Simultaneously DNIC enhanced the resistance of isolated heart and the organism as a whole to damaging effects of intracellular calcium overload induced by post-ischemic reperfusion or vigorous exercise, respectively [11].

References