Crucial role of lysosomal iron in the formation of dinitrosyl iron complexes in vivo

Lewandowska, Hanna; Męczyńska, Sylwia; Sochanowicz, Barbara; Sadło, Jarosław; Kruszewski, Marcin

doi:10.1007/s00775-006-0192-8

Cited by 28 publications

(23 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5), SIH does not completely prevent DNIC formation from •NO and SIH-resistant DNIC may well be capable of transnitrosating thiols. Other studies have demonstrated SIH-inhibitable and SIH-resistant DNIC formation in cells (29,30).…”

Section: Discussionmentioning

confidence: 88%

Dinitrosyliron complexes and the mechanism(s) of cellular protein nitrosothiol formation from nitric oxide

Bosworth

Toledo

Żmijewski

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

196

221

View full text Add to dashboard Cite

Nitrosothiols (RSNO), formed from thiols and metabolites of nitric oxide (•NO), have been implicated in a diverse set of physiological and pathophysiological processes, although the exact mechanisms by which they are formed biologically are unknown. Several candidate nitrosative pathways involve the reaction of •NO with O 2, reactive oxygen species (ROS), and transition metals. We developed a strategy using extracellular ferrocyanide to determine that under our conditions intracellular protein RSNO formation occurs from reaction of •NO inside the cell, as opposed to cellular entry of nitrosative reactants from the extracellular compartment. Using this method we found that in RAW 264.7 cells RSNO formation occurs only at very low (<8 M) O2 concentrations and exhibits zero-order dependence on •NO concentration. Indeed, RSNO formation is not inhibited even at O 2 levels <1 M. Additionally, chelation of intracellular chelatable iron pool (CIP) reduces RSNO formation by >50%. One possible metal-dependent, O 2-independent nitrosative pathway is the reaction of thiols with dinitrosyliron complexes (DNIC), which are formed in cells from the reaction of •NO with the CIP. Under our conditions, DNIC formation, like RSNO formation, is inhibited by Ϸ50% after chelation of labile iron. Both DNIC and RSNO are also increased during overproduction of ROS by the redox cycler 5,8-dimethoxy-1,4-naphthoquinone. Taken together, these data strongly suggest that cellular RSNO are formed from free •NO via transnitrosation from DNIC derived from the CIP. We have examined in detail the kinetics and mechanism of RSNO formation inside cells.iron ͉ nitrosation ͉ reactive nitrogen species ͉ reactive oxygen species ͉ chelatable iron N itric oxide (nitrogen monoxide, •NO) is a ubiquitous signaling molecule that originally was thought to exert its effects solely through interaction with transition metal ligands of proteins, most notably the heme group of soluble guanylate cyclase. However, it is now recognized that •NO is capable of affecting cell physiology by inducing oxidative and covalent modification of protein amino acid residues. One such modification, S-nitrosation, the addition of a nitroso group to a thiol to form a nitrosothiol (RSNO), has received considerable attention as a potentially important posttranslational protein modification. S-nitrosated products are found ubiquitously in vivo (1), and thiol nitrosation has been found to alter the activity of a diverse set of proteins and may therefore represent an important concept in cellular and organismal biology (2).A central issue in this paradigm is understanding the routes by which RSNO are formed inside cells. Importation of low molecular weight (LMW) RSNO through LAT transporters, followed by transnitrosation reactions, have been demonstrated to be a potent route for intracellular RSNO formation (3). However, mechanisms of de novo synthesis from free •NO are less clear. Proposed mechanisms include the reaction of •NO with O 2 (autoxidation), either in the aqueous phase (4) or in ...

show abstract

Section: Discussionmentioning

confidence: 88%

Dinitrosyliron complexes and the mechanism(s) of cellular protein nitrosothiol formation from nitric oxide

Bosworth

Toledo

Żmijewski

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

196

221

View full text Add to dashboard Cite

show abstract

“…The formation of complex 4 was also characterized by single-crystal X-ray diffraction ( Figure S4 in the Supporting Information), and the by-product carbazole was identified by 1 H NMR spectroscopy. The released nitric oxide in the reaction of complex 1 and (PyPepS) 2 was trapped by complex [S 5 FeA C H T U N G T R E N N U N G (m-S) 2 FeS 5 ] 2À to produce the known [S 5 Fe(NO) 2 ] À . [24] The transformation of complex 1 into complex 4, carbazole, and NO (g) under the reaction of (PyPepS) 2 and 1 may be accounted for by the following reaction sequences: (PyPepS) 2 was oxidatively added to 1, thus leading to the formation of intermediate B www.chemeurj.org (Scheme 2).…”

Section: Resultsmentioning

confidence: 99%

“…Also, nonheme iron centers (i.e., [FeÀS] clusters) play sensory and regulatory roles in transducing the NO signal to modulate cellular iron homeostasis and alter the metabolism of bacteria. [5,6] In addition, nitroxyl (HNO), which converts rapidly to N 2 O in aqueous solution, undergoes addition to protein thiols to result in Abstract: Release of the distinct NO redox-interrelated forms (NO + , CNO, and HNO/NO À ), derived from reaction of the dinitrosyl iron complex (DNIC) [(NO) 2 FeA C H T U N G T R E N N U N G (C 12 H 8 N) 2 ] À (1) (C 12 sulfhydryl oxidation through the proposed N-hydroxysulfenamide intermediate RSNHOH. [7] S-nitrosation has emerged as a post-translational modification of proteins by covalent attachment of a nitroso group to the thiol side chain of cysteine to convey part of the ubiquitous influence of nitric oxide on cellular signal transduction.…”

Section: Introductionmentioning

confidence: 99%

Formation of the Distinct Redox‐Interrelated Forms of Nitric Oxide from Reaction of Dinitrosyl Iron Complexes (DNICs) and Substitution Ligands

Chen

Liaw

2010

Chemistry A European J

View full text Add to dashboard Cite

Release of the distinct NO redox-interrelated forms (NO(+), *NO, and HNO/NO(-)), derived from reaction of the dinitrosyl iron complex (DNIC) [(NO)(2)Fe(C(12)H(8)N)(2)](-) (1) (C(12)H(8)N=carbazolate) and the substitution ligands (S(2)CNMe(2))(2), [SC(6)H(4)-o-NHC(O)(C(5)H(4)N)](2) ((PyPepS)(2)), and P(C(6)H(3)-3-SiMe(3)-2-SH)(3) ([P(SH)(3)]), respectively, was demonstrated. In contrast to the reaction of (PyPepS)(2) and DNIC 1 in a 1:1 stoichiometry that induces the release of an NO radical and the formation of complex [PPN][Fe(PyPepS)(2)] (4), the incoming substitution ligand (S(2)CNMe(2))(2) triggered the transformation of DNIC 1 into complex [(NO)Fe(S(2)CNMe(2))(2)] (2) along with N-nitrosocarbazole (3). The subsequent nitrosation of N-acetylpenicillamine (NAP) by N-nitrosocarbazole (3) to produce S-nitroso-N-acetylpenicillamine (SNAP) may signify the possible formation pathway of S-nitrosothiols from DNICs by means of transnitrosation of N-nitrosamines. Protonation of DNIC 1 by [P(SH)(3)] triggers the release of HNO and the generation of complex [PPN][Fe(NO)P(C(6)H(3)-3-SiMe(3)-2-S)(3)] (5). In a similar fashion, the nucleophilic attack of the chelating ligand P(C(6)H(3)-3-SiMe(3)-2-SNa)(3) ([P(SNa)(3)]) on DNIC 1 resulted in the direct release of [NO](-) captured by [((15)NO)Fe(SPh)(3)](-), thus leading to [((15)NO)((14)NO)Fe(SPh)(2)](-). These results illustrate one aspect of how the incoming substitution ligands ((S(2)CNMe(2))(2) vs. (PyPepS)(2) vs. [P(SH)(3)]/[P(SNa)(3)]) in cooperation with the carbazolate-coordinated ligands of DNIC 1 function to control the release of NO(+), *NO, or [NO](-) from DNIC 1 upon reaction of complex 1 and the substitution ligands. Also, these results signify that DNICs may act as an intermediary of NO in the redox signaling processes by providing the distinct redox-interrelated forms of NO to interact with different NO-responsive targets in biological systems.

show abstract

“…In vitro/vivo, both protein-bound DNICs and LMW DNICs are possibly identified and characterized by their distinctive electron paramagnetic resonance (EPR) signals at g = 2.03 [14][15][16][17]. In spite of the major thiol components of cellular DNICs composed of cysteine and glutathione in vivo [18], the DNICs ligated by cysteinate, histidine, deprotonated imidazole, and tyrosinate were found and proposed in enzymology based on EPR spectra [11,[19][20][21][22][23][24]. Recently, the protein-bound DNIC with one sulfur atom of the glutathione and one oxygen atom of the tyrosine bound to the {Fe(NO) 2 } core has been well characterized by X-ray diffraction study via the addition of a dinitrosyldiglutathionyl iron complex into human glutathione transferase P1-1 in vitro/vivo [21].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and reactivity of the five-coordinate {Fe(NO)2}9 [(TMEDA)Fe(NO)2I]

Chen

Lee

2009

Journal of Organometallic Chemistry

View full text Add to dashboard Cite

Crucial role of lysosomal iron in the formation of dinitrosyl iron complexes in vivo

Cited by 28 publications

References 53 publications

Dinitrosyliron complexes and the mechanism(s) of cellular protein nitrosothiol formation from nitric oxide

Dinitrosyliron complexes and the mechanism(s) of cellular protein nitrosothiol formation from nitric oxide

Formation of the Distinct Redox‐Interrelated Forms of Nitric Oxide from Reaction of Dinitrosyl Iron Complexes (DNICs) and Substitution Ligands

Synthesis and reactivity of the five-coordinate {Fe(NO)2}9 [(TMEDA)Fe(NO)2I]

Contact Info

Product

Resources

About