Physical properties of dinitrosyl iron complexes with thiol-containing ligands in relation with their vasodilator activity

Vanin, Anatoly F.; Stukan, R. A.; Манухина, Е. Б.

doi:10.1016/0167-4838(95)00247-2

Cited by 89 publications

(51 citation statements)

References 9 publications

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“…These results show that ⅐ NO and DFO compete for the same iron pool and that CIP is quantitatively converted to DNIC upon ⅐ NO addition. This result also reveals that the resultant iron-nitrosyl complexes are virtually all paramagnetic species (as opposed to the multiple possible diamagnetic species) (32). In addition, the primary iron source for cellular DNIC is the CIP and not prosthetic iron such as iron-sulfur clusters, because the CIP is by definition a "loosely bound" iron (6).…”

Section: Discussionmentioning

confidence: 72%

Nitric Oxide-induced Conversion of Cellular Chelatable Iron into Macromolecule-bound Paramagnetic Dinitrosyliron Complexes

Toledo

Bosworth

Hennon

et al. 2008

Journal of Biological Chemistry

107

139

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One of the most important biological reactions of nitric oxide (nitrogen monoxide, ⅐ NO) is its reaction with transition metals, of which iron is the major target. This is confirmed by the ubiquitous formation of EPR-detectable g ‫؍‬ 2.04 signals in cells, tissues, and animals upon exposure to both exogenous and endogenous ⅐ NO. The source of the iron for these dinitrosyliron complexes (DNIC), and its relationship to cellular iron homeostasis, is not clear. Evidence has shown that the chelatable iron pool (CIP) may be at least partially responsible for this iron, but quantitation and kinetic characterization have not been reported. In the murine cell line RAW 264.7, ⅐ NO reacts with the CIP similarly to the strong chelator salicylaldehyde isonicotinoyl hydrazone (SIH) in rapidly releasing iron from the iron-calcein complex. SIH pretreatment prevents DNIC formation from ⅐ NO, and SIH added during the ⅐ NO treatment "freezes" DNIC levels, showing that the complexes are formed from the CIP, and they are stable (resistant to SIH). DNIC formation requires free ⅐ NO, because addition of oxyhemoglobin prevents formation from either ⅐ NO donor or S-nitrosocysteine, the latter treatment resulting in 100-fold higher intracellular nitrosothiol levels. EPR measurement of the CIP using desferroxamine shows quantitative conversion of CIP into DNIC by ⅐ NO. In conclusion, the CIP is rapidly and quantitatively converted to paramagnetic large molecular mass DNIC from exposure to free ⅐ NO but not from cellular nitrosothiol. These results have important implications for the antioxidative actions of ⅐ NO and its effects on cellular iron homeostasis.Nitric oxide (nitrogen monoxide, ⅐ NO) is a multifunctional small radical molecule responsible for a remarkable array of physiological and pathophysiological phenomena (1). Although ⅐ NO gives rise to a complex array of reactive species (2) in the biological milieu, ⅐ NO itself reacts directly with only a small number of targets. These targets are either species with unpaired electrons or transition metals; the origin of this reactivity pattern lies in the ability of these targets to stabilize the unpaired electron on ⅐ NO. In the case of transition metals, this stabilization occurs because of the strong interaction of ⅐ NO orbitals and the metal d-orbitals (3). Formation of metal-nitrosyls in biological systems can give rise to several paramagnetic species, which can be observed by EPR spectroscopy, and has been utilized to glean important information regarding the biological actions of ⅐ NO (4). In particular, exposure of cells or tissues to ⅐ NO (either exogenously administered or endogenously synthesized) results in the ubiquitous appearance of a "g ϭ 2.04" axial EPR signal, which has been assigned to iron in square planar coordination with two nitrosyl ligands (denoted "dinitrosyliron complexes" (DNIC) 3 (5). The source of this iron, the nature of the other iron ligands, and the origin of their formation are not clear.The intracellular labile or chelatable iron pool (CIP) is a smal...

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Section: Discussionmentioning

confidence: 72%

Nitric Oxide-induced Conversion of Cellular Chelatable Iron into Macromolecule-bound Paramagnetic Dinitrosyliron Complexes

Toledo

Bosworth

Hennon

et al. 2008

Journal of Biological Chemistry

107

139

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“…NO and free iron may also form complexes with low molecular weight thiols like glutathione and cysteine (62)(63)(64). These dinitrosyl-iron complexes are relatively stable in contrast to the highly reactive free NO molecule (65,66) and were shown to be potential NO carrier molecules in mammals (62). In plants, interactions of NO with hemes (67-69) or iron-sulfur clusters (70), and S-nitrosylation reactions (71) have been shown, and dinitrosyl-iron complexes have been detected (72).…”

Section: Discussionmentioning

confidence: 99%

An Iron-induced Nitric Oxide Burst Precedes Ubiquitin-dependent Protein Degradation for Arabidopsis AtFer1 Ferritin Gene Expression

Arnaud

Murgia²,

Boucherez³

et al. 2006

Journal of Biological Chemistry

170

109

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Ferritins play an essential role in iron homeostasis by sequestering iron in a bioavailable and non-toxic form. In plants, ferritin mRNAs are highly and quickly accumulated in response to iron overload. Such accumulation leads to a subsequent ferritin protein synthesis and iron storage, thus avoiding oxidative stress to take place. By combining pharmacological and imaging approaches in an Arabidopsis cell culture system, we have identified several elements in the signal transduction pathway leading to the increase of AtFer1 transcript level after iron treatment. Nitric oxide quickly accumulates in the plastids after iron treatment. This compound acts downstream of iron and upstream of a PP2A-type phosphatase to promote an increase of AtFer1 mRNA level. The AtFer1 gene transcription has been previously shown to be repressed under low iron conditions with the involvement of the cis-acting element iron-dependent regulatory sequence identified within the AtFer1 promoter sequence. We show here that the repressor is unlikely a transcription factor directly bound to the iron-dependent regulatory sequence; such a repressor is ubiquitinated upon iron treatment and subsequently degraded through a 26 S proteasome-dependent pathway.As the major cofactor of proteins involved in essential processes like photosynthesis, respiration, DNA replication, or nitrogen fixation, iron is an essential element for life. Nonetheless, in the free ionic form, iron is toxic as it can catalyze the formation of reactive oxygen species through the Fenton reaction. These reactive oxygen species damage the cell membranes, DNA, and proteins (1, 2). Thus, iron homeostasis has to be tightly regulated, to avoid starvation that impairs the metabolism, and to avoid excess that may lead to cell death. Iron homeostasis is strongly dependent on ferritins, which are ironstorage proteins, found in bacteria, animals, and plants. Plant and animal ferritin structures are very similar, and are formed by 24 subunits arranged to form a hollow sphere able to sequester iron in a non-toxic and bioavailable form (3).In animals, ferritin synthesis is mainly regulated at the posttranscriptional level (3, 4). Ferritin mRNAs contain iron-responsive elements in their 5Ј-untranslated regions that function as binding sites for two related trans-acting factors, namely iron regulatory proteins IRP1 and IRP2. When bound to the iron-responsive element in the ferritin mRNA, the IRP inhibit translation of the transcript (4). IRP1 is a bifunctional protein that when iron is abundant possesses a 4Fe-4S cluster and acts as cytoplasmic aconitase. When iron levels are low, the 4Fe-4S cluster disassembles and the apoprotein acquires IRP 3 activity, thus repressing ferritin translation. High levels of iron lead to the 4Fe-4S cluster reconstitution and therefore the protein aconitase activity. In contrast to IRP1, IRP2 cannot assemble a iron-sulfur cluster and lacks aconitase activity. IRP2 shares about 60% amino acid sequence identity with IRP1, but differs only in having a 73-amino aci...

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“…67 They can be used for the design of a new class of cardiovascular drugs, as animal tests have shown them to manifest a vasodilatory effect. [68][69][70][71] Mononuclear Dinuclear…”

Section: Diazenium 12 Diolates R-[n(o)-no] -(Nonoates)mentioning

confidence: 99%

Functional models of [Fe—S] nitrosyl proteins

Санина

Алдошин

2004

Russ Chem Bull

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Physical properties of dinitrosyl iron complexes with thiol-containing ligands in relation with their vasodilator activity

Cited by 89 publications

References 9 publications

Nitric Oxide-induced Conversion of Cellular Chelatable Iron into Macromolecule-bound Paramagnetic Dinitrosyliron Complexes

Nitric Oxide-induced Conversion of Cellular Chelatable Iron into Macromolecule-bound Paramagnetic Dinitrosyliron Complexes

An Iron-induced Nitric Oxide Burst Precedes Ubiquitin-dependent Protein Degradation for Arabidopsis AtFer1 Ferritin Gene Expression

Functional models of [Fe—S] nitrosyl proteins

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