Iron Catalyzes both Decomposition and Synthesis ofS-Nitrosothiols: Optical and Electron Paramagnetic Resonance Studies

Vanin, Anatoly F.; Malenkova, Irina V.; Сереженков, В. А.

doi:10.1006/niox.1997.0122

Cited by 184 publications

(167 citation statements)

References 34 publications

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“…After treatment with 10 M (1,19,20). These results show that the mechanism responsible for RSNO formation is only slowly reversible and that the increase in RSNO levels ( (21), which in acellular systems are capable of nitrosative chemistry (8,9). DNICs in cells exposed to •NO are formed from the CIP (22), representing a small (Ϸ5%) fraction of total iron thought to be in transit between the various cellular iron pools (23).…”

Section: •No Exposure Results Inmentioning

confidence: 89%

“…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 an accelerated manner in hydrophobic phases (5) (7), and the interaction between •NO and transition metals and/or metalloproteins (8)(9)(10)(11)(12)(13)(14).In this study, we examine the contributions of potential nitrosative pathways in RAW 264.7 murine macrophages. We present evidence suggesting that dinitrosyliron complexes (DNICs) formed at least in part from the cellular chelatable iron pool (CIP), through an O 2 -independent transnitrosative process, are responsible for the majority of RSNO formation in cells, and that reactive oxygen species (ROS) enhance RSNO formation, possibly via increases in DNICs.…”

mentioning

confidence: 99%

“…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 an accelerated manner in hydrophobic phases (5); reaction of •NO with a thiol in the presence of a cellular electron acceptor (6); reaction between •NO and superoxide (O 2 •Ϫ ) in the presence of excess •NO (7), and the interaction between •NO and transition metals and/or metalloproteins (8)(9)(10)(11)(12)(13)(14).…”

mentioning

confidence: 99%

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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.

198

221

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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 ...

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Section: •No Exposure Results Inmentioning

confidence: 89%

mentioning

confidence: 99%

“…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 an accelerated manner in hydrophobic phases (5); reaction of •NO with a thiol in the presence of a cellular electron acceptor (6); reaction between •NO and superoxide (O 2 •Ϫ ) in the presence of excess •NO (7), and the interaction between •NO and transition metals and/or metalloproteins (8)(9)(10)(11)(12)(13)(14).…”

mentioning

confidence: 99%

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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.

198

221

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“…Due to the high concentration of Hb within the midgut, it is reasonable to propose that the predominant metal nitrosyl is iron nitrosylHb. Alternatively, iron released from Hb during digestion prior to sequestration in hematin could react with · NO to form dinitrosyl iron complexes (DNICs) [29]. DNICs, although perhaps formed at lower levels than iron nitrosylHb, could mediate toxic effects through redox destabilization [30].…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide metabolites induced in Anopheles stephensi control malaria parasite infection

Peterson

Gow

Luckhart

2007

Free Radical Biology and Medicine

100

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Malaria parasite infection in anopheline mosquitoes is limited by inflammatory levels of nitric oxide metabolites. To assess the mechanisms of parasite stasis or toxicity, we investigated the biochemistry of these metabolites within the blood-filled mosquito midgut. Our data indicate that nitrates, but not nitrites, are elevated in the Plasmodium-infected midgut. Although levels of S-nitrosothiols do not change with infection, blood proteins are S-nitrosylated after ingestion by the mosquito. In addition, photolyzable nitric oxide, which can be attributed to metal nitrosyls, is elevated following infection and, based on the abundance of hemoglobin, likely includes heme iron nitrosyl. The persistance of oxyhemoglobin throughout blood digestion and changes in hemoglobin conformation in response to infection suggest that hemoglobin catalyzes the synthesis of nitric oxide metabolites in a reducing environment. Provision of urate, a potent reductant and scavenger of oxidants and nitrating agents, as a dietary supplement to mosquitoes increased parasite infection levels relative to allantoin-fed controls, suggesting that nitrosative and/or oxidative stresses negatively impact developing parasites. Collectively, our results reveal a unique role for nitric oxide in an oxyhemoglobin-rich environment. In contrast to facilitating oxygen delivery by hemoglobin in the mammalian vasculature, nitric oxide synthesis in the blood-filled mosquito midgut drives the formation of toxic metabolites that limit parasite development.

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“…Denitrosation by external denitrosilase leads to a rapid decrease in the fraction of the nitrosated residues and might induce an intermittent flow of nitrite or thionitrites. The information acquired previously in response to a signal from outside (denitrosilase) is also processed and transmitted to neighbouring structures as a nitrite or RSNO flow, which can be reduced back to NO (23)(24)(25)(26).…”

Section: Resultsmentioning

confidence: 99%

Structural Features of Proteins Responsible for Resistance of Tryptophan Residues to Nitrosylation

Suntsova

Nedospasov

2002

IUBMB Life

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Iron Catalyzes both Decomposition and Synthesis ofS-Nitrosothiols: Optical and Electron Paramagnetic Resonance Studies

Cited by 184 publications

References 34 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

Nitric oxide metabolites induced in Anopheles stephensi control malaria parasite infection

Structural Features of Proteins Responsible for Resistance of Tryptophan Residues to Nitrosylation

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