The Specificity of Nitroxyl Chemistry Is Unique Among Nitrogen Oxides in Biological Systems

Flores-Santana, Wilmarie; Salmon, Debra J.; Donzelli, Sonia; Switzer, Christopher; Basudhar, Debashree; Ridnour, Lisa A.; Cheng, Robert; Glynn, Sharon A.; Paolocci, Nazareno; Fukuto, Jon M.; Miranda, Katrina M.; Wink, David A.

doi:10.1089/ars.2010.3841

Cited by 94 publications

(99 citation statements)

References 172 publications

(183 reference statements)

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“…In the set of extracytoplasmic proteins that were observed exclusively in NDFO cultures (see Data Set S1E), only a few peptides were observed, but efflux pumps are highly represented. The expression of heavy metal efflux pumps in response to anaerobic Fe(II) stress is a novel finding and suggests that these proteins may be involved in the export of metals other than those commonly considered to be substrates (40,41). Furthermore, because the RND family efflux pumps identified in A. ebreus are proton/solute antiporters, the energy cost is putatively less than that of an ATP-consuming transporter and RND family efflux pumps are able to load substrate from either the periplasm or the cytoplasm (42).…”

Section: Evidence Against An Inducible Fe(ii) Oxidoreductase Inmentioning

confidence: 99%

Fe(II) Oxidation Is an Innate Capability of Nitrate-Reducing Bacteria That Involves Abiotic and Biotic Reactions

Carlson

Clark²,

Blazewicz³

et al. 2013

Journal of Bacteriology

148

160

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Phylogenetically diverse species of bacteria can catalyze the oxidation of ferrous iron [Fe(II)] coupled to nitrate (NO 3؊ ) reduction, often referred to as nitrate-dependent iron oxidation (NDFO). Very little is known about the biochemistry of NDFO, and though growth benefits have been observed, mineral encrustations and nitrite accumulation likely limit growth. Acidovorax ebreus, like other species in the Acidovorax genus, is proficient at catalyzing NDFO. Our results suggest that the induction of specific Fe(II) oxidoreductase proteins is not required for NDFO. No upregulated periplasmic or outer membrane redox-active proteins, like those involved in Fe(II) oxidation by acidophilic iron oxidizers or anaerobic photoferrotrophs, were observed in proteomic experiments. We demonstrate that while "abiotic" extracellular reactions between Fe(II) and biogenic NO 2 ؊ /NO can be involved in NDFO, intracellular reactions between Fe(II) and periplasmic components are essential to initiate extensive NDFO. We present evidence that an organic cosubstrate inhibits NDFO, likely by keeping periplasmic enzymes in their reduced state, stimulating metal efflux pumping, or both, and that growth during NDFO relies on the capacity of a nitrate-reducing bacterium to overcome the toxicity of Fe(II) and reactive nitrogen species. On the basis of our data and evidence in the literature, we postulate that all respiratory nitrate-reducing bacteria are innately capable of catalyzing NDFO. Our findings have implications for a mechanistic understanding of NDFO, the biogeochemical controls on anaerobic Fe(II) oxidation, and the production of NO 2 ؊ , NO, and N 2 O in the environment.

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Section: Evidence Against An Inducible Fe(ii) Oxidoreductase Inmentioning

confidence: 99%

Fe(II) Oxidation Is an Innate Capability of Nitrate-Reducing Bacteria That Involves Abiotic and Biotic Reactions

Carlson

Clark²,

Blazewicz³

et al. 2013

Journal of Bacteriology

148

160

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“…Unlike NO•, HNO is resistant to ROS scavenging, does not develop tolerance to its actions, and may target oxidized sGC. 9,12,19,44,45 HNO also has a unique ability to enhance LV function, 8,16,46,47 considered dependent on both sGC-independent and sGC-dependent mechanisms. …”

Section: -Nca Treatment Protects Against Diabetes Mellitus-induced Cmentioning

confidence: 99%

Chronic Administration of the Nitroxyl Donor 1-Nitrosocyclo Hexyl Acetate Limits Left Ventricular Diastolic Dysfunction in a Mouse Model of Diabetes Mellitus In Vivo

Cao

Wong

Rosli

et al. 2015

Circ: Heart Failure

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Background-Nitroxyl (HNO), a redox congener of nitric oxide (NO•), is a novel regulator of cardiovascular function, combining concomitant positive inotropic, lusitropic, and vasodilator properties. Moreover, HNO exhibits myocardial antihypertrophic and superoxide-suppressing actions. Despite these favorable actions, the impact of chronic HNO administration has yet to be reported in the context of cardiomyopathy. Diabetic cardiomyopathy is characterized by early diastolic dysfunction and adverse left ventricular (LV) structural remodeling, with LV superoxide generation playing a major causal role. We tested the hypothesis that the HNO donor 1-nitrosocyclohexylacetate (1-NCA) limits cardiomyocyte hypertrophy and LV diastolic dysfunction in a mouse model of diabetes mellitus in vivo. Methods and Results-Diabetes mellitus was induced in male FVB/N mice using streptozotocin. After 4 weeks, diabetic and nondiabetic mice were allocated to 1-NCA therapy (83 mg/kg per day IP) or vehicle and followed up for a further 4 weeks. Diabetes mellitus-induced LV diastolic dysfunction was evident on echocardiography-derived E and A wave velocities, E:A ratio, deceleration, and isovolumic relaxation times; LV systolic function was preserved. Increased LV cardiomyocyte size, hypertrophic and profibrotic gene expression, and upregulation of LV superoxide were also evident. These characteristics of diabetic cardiomyopathy were largely prevented by 1-NCA treatment. Selectivity of 1-NCA as an HNO donor was demonstrated by sensitivity of acute 1-NCA to L-cysteine but not to hydroxocobalamin in the normal rat heart ex vivo. Conclusions-Our studies provide the first evidence that HNO donors may represent a promising strategy for treatment of diabetic cardiomyopathy and implies therapeutic efficacy in settings of chronic heart failure. (Circ Heart Fail. 2015;8:572-581.

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“…At pH 6, cyanide protonation favors the predominance of the tetracyano-over the pentacyano-complex. 3 On the basis of finding cation catalysis, it has been demonstrated that these reactions may be considered as outer-sphere as far as the cyanometallate ions are concerned but in which a partially desolvated cation bridges the reacting anions [74]. It has been found that the [Fe III (CN) 6 ] 3-ion reacts with free HNO (derived from Angeli's salt, at pH 7) forming [Fe II (CN) 6 ] 4-and NO.…”

Section: Electrochemical Reactivity Of (I)mentioning

confidence: 99%

“…A specific focus on the one-electron reduction product of NO, the nitroxyl species HNO/NO - [3,4], was a mandatory consequence of its suspected intermediacy in NO biochemistry. The synthetic aspects, spectroscopic characterization and reactivity of free aqueous HNO have been early considered [5].…”

Section: Introductionmentioning

confidence: 99%

Reactivity of iron(II)-bound nitrosyl hydride (HNO, nitroxyl) in aqueous solution

Montenegro¹,

Bari²,

Olabe³

2013

Journal of Inorganic Biochemistry

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The Specificity of Nitroxyl Chemistry Is Unique Among Nitrogen Oxides in Biological Systems

Cited by 94 publications

References 172 publications

Fe(II) Oxidation Is an Innate Capability of Nitrate-Reducing Bacteria That Involves Abiotic and Biotic Reactions

Fe(II) Oxidation Is an Innate Capability of Nitrate-Reducing Bacteria That Involves Abiotic and Biotic Reactions

Chronic Administration of the Nitroxyl Donor 1-Nitrosocyclo Hexyl Acetate Limits Left Ventricular Diastolic Dysfunction in a Mouse Model of Diabetes Mellitus In Vivo

Reactivity of iron(II)-bound nitrosyl hydride (HNO, nitroxyl) in aqueous solution

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