Reaction between <i>S</i>-Nitrosothiols and Thiols:  Generation of Nitroxyl (HNO) and Subsequent Chemistry

Wong, Patrick; Hyun, Jinjoo; Fukuto, Jon M.; Shirota, Frances N.; DeMaster, Eugene G.; Shoeman, Don W.; Nagasawa, H. T.

doi:10.1021/bi9850569

Cited by 76 publications

(151 citation statements)

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“…Joseph Saavedra and Larry Keefer (Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick). Sulfinamide was synthesized as previously described [33,35]. Stock solutions of NO were prepared by sparging argon-deaerated 100 mM phosphate buffer (pH 7.4) with hydroxide scrubbed NO (>99%; Matheson, Montgomeryville, PA).…”

Section: Experimental Procedures Materialsmentioning

confidence: 99%

Generation of nitroxyl by heme protein-mediated peroxidation of hydroxylamine but not N-hydroxy-L-arginine

Donzelli

Espey

Flores-Santana

et al. 2008

Free Radical Biology and Medicine

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The chemical reactivity, toxicology and pharmacological responses to nitroxyl (HNO) are often distinctly different from those of nitric oxide (NO). The discovery that HNO donors may have pharmacological utility for treatment of cardiovascular disorders such as heart failure and ischemia reperfusion has led to increased speculation of potential endogenous pathways for HNO biosynthesis. Here, the ability of heme proteins to utilize H 2 O 2 to oxidize hydroxylamine (NH 2 OH) or N-hydroxy-L-arginine (NOHA) to HNO was examined. Formation of HNO was evaluated with a recently developed selective assay in which the reaction products in the presence of reduced glutathione (GSH) were quantified by HPLC. Release of HNO from the heme pocket was indicated by formation of sulfinamide (GS(O)NH 2 ), while the yields of nitrite and nitrate signified the degree of intramolecular recombination of HNO with the heme. Formation of GS(O)NH 2 was observed upon oxidation of NH 2 OH, whereas NOHA, the primary intermediate in oxidation of L-arginine by NO synthase, was apparently resistant to oxidation by the heme proteins utilized. In the presence of NH 2 OH, the highest yields of GS(O)NH 2 were observed with proteins in which the heme was coordinated to a histidine (horseradish peroxidase, lactoperoxidase, myeloperoxidase, myoglobin and hemoglobin) in contrast to a tyrosine (catalase) or cysteine (cytochrome P450). That peroxidation of NH 2 OH by horseradish peroxidase produced free HNO, which was able to affect intracellular targets, was verified by conversion of 4,5-diaminofluorescein to the corresponding fluorophore within intact cells.

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Section: Experimental Procedures Materialsmentioning

confidence: 99%

Generation of nitroxyl by heme protein-mediated peroxidation of hydroxylamine but not N-hydroxy-L-arginine

Donzelli

Espey

Flores-Santana

et al. 2008

Free Radical Biology and Medicine

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“…to proceed via reduction of NO • by SOD, [42] ferrocytochrome c, [43] and ubiquinol, [44] and/or reduction of GSNO by GSH and the alcohol dehydrogenase system. [45][46][47] Several groups have reported that HNO, per se a strong reductant, [48] can trigger reactions of oxidation.…”

Section: Chemical Fate Of No• In Biological Systemsmentioning

confidence: 99%

Inflammatory Modulation of Hepatocyte Apoptosis by Nitric Oxide: In Vivo, In Vitro, and In Silico Studies

Vodovotz¹,

Kim²,

Bagci³

et al. 2004

CMM

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“…However, the chemistries of HNO and PN differ, and some studies have noted that toxicities of these compounds derive from different reactive intermediates [53]. For example, HNO has a high affinity for GSH [54]; exposure of cells to millimolar concentrations of AS can dramatically reduce intracellular GSH through the production of GSNHOH [51,53]. As such, Prxs may function to protect cells through direct recycling of oxidized thiols to maintain cellular homeostasis [55] in mosquito cells.…”

mentioning

confidence: 99%

A mosquito 2-Cys peroxiredoxin protects against nitrosative and oxidative stresses associated with malaria parasite infection

Peterson

Luckhart

2006

Free Radical Biology and Medicine

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Malaria parasite infection in anopheline mosquitoes induces nitrosative and oxidative stresses that limit parasite development, but also damage mosquito tissues in proximity to the response. Based on these observations, we proposed that cellular defenses in the mosquito may be induced to minimize self-damage. Specifically, we hypothesized that peroxiredoxins (Prxs), enzymes known to detoxify reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS), protect mosquito cells. We identified an Anopheles stephensi 2-Cys Prx ortholog of Drosophila melanogaster Prx-4783, which protects fly cells against oxidative stresses. To assess function, AsPrx-4783 was overexpressed in D. melanogaster (S2) and in A. stephensi (MSQ43) cells and silenced in MSQ43 cells with RNA interference before treatment with various ROS and RNOS. Our data revealed that AsPrx-4783 and DmPrx-4783 differ in host cell protection and that AsPrx-4783 protects A. stephensi cells against stresses that are relevant to malaria parasite infection in vivo, namely nitric oxide (NO), hydrogen peroxide, nitroxyl, and peroxynitrite. Further, AsPrx-4783 expression is induced in the mosquito midgut by parasite infection at times associated with peak nitrosative and oxidative stresses. Hence, whereas the NO-mediated defense response is toxic to both host and parasite, AsPrx-4783 may shift the balance in favor of the mosquito. KeywordsMalaria; Mosquito; Peroxiredoxin; Plasmodium; Anopheles; Nitric oxide; Nitrosative stress; Free radicals It has long been recognized that reactive oxygen species (ROS) and, more recently, reactive nitrogen oxide species (RNOS) function to defend hosts against pathogens [1]. Although ROS and RNOS are cytotoxic to pathogens and parasites, they also induce oxidative and nitrosative stresses in the host and can damage host tissues [1]. Host protection against oxidative and nitrosative stress, therefore, is vital for homeostasis and hence survival. Gene products that confer protection against ROS are well known. In contrast, gene products that confer protection against RNOS have been identified, but are less well studied. The peroxiredoxins (Prxs) are a recently discovered family of antioxidant peroxidases that can reduce hydrogen peroxide and alkyl hydroperoxides to water and the corresponding alcohols, respectively, and can protect cells from widely divergent organisms against a variety of nitrosative stress challenges [2][3][4][5][6].Prxs do not show sequence homology to other known antioxidant enzymes. Crystal structures of PrxI, II, V, and VI have revealed that Prxs are novel members of the thioredoxin fold * Corresponding author. Fax: +1 530 752 8692. E-mail address: sluckhart@ucdavis.edu (S. Luckhart). NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript superfamily [7,8]. Unlike most peroxidases-which contain a heme ring at their active site (e.g., cytochrome c peroxidase) or a redox-sensitive moiety like selenocysteine (glutathione peroxidase; GPx), vanadium (algal bro...

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Reaction between S-Nitrosothiols and Thiols: Generation of Nitroxyl (HNO) and Subsequent Chemistry

Cited by 76 publications

References 0 publications

Generation of nitroxyl by heme protein-mediated peroxidation of hydroxylamine but not N-hydroxy-L-arginine

Generation of nitroxyl by heme protein-mediated peroxidation of hydroxylamine but not N-hydroxy-L-arginine

Inflammatory Modulation of Hepatocyte Apoptosis by Nitric Oxide: In Vivo, In Vitro, and In Silico Studies

A mosquito 2-Cys peroxiredoxin protects against nitrosative and oxidative stresses associated with malaria parasite infection

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