The Chemistry of Protein Modifications Elicited by Nitric Oxide and Related Nitrogen Oxides

Thomas, Douglas D.; Ridnour, Lisa A.; Donzelli, Sonia; Espey, Michael Graham; Mancardi, Daniele; Isenberg, Jeffery S.; Feelisch, Martin; Roberts, David D.; Wink, David A.

doi:10.1002/0471973122.ch2

Cited by 8 publications

(9 citation statements)

References 145 publications

(196 reference statements)

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“…The antioxidant potential of NO has been discussed in eukaryotic systems, where NO reduces the oxidizing capacity of reactive oxygen and nitrogen species and modulates cellular and physiological processes that prevent cell and tissue injury (95,99). Our results strongly indicate that NO can also function as a protein protection determinant in bacteria.…”

Section: Vol 190 2008 Nitric Oxide Stress In B Subtilis and S Aurmentioning

confidence: 57%

Nitric Oxide Stress Induces Different Responses but Mediates Comparable Protein Thiol Protection inBacillus subtilisandStaphylococcus aureus

et al. 2008

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The nonpathogenic Bacillus subtilis and the pathogen Staphylococcus aureus are gram-positive model organisms that have to cope with the radical nitric oxide (NO) generated by nitrite reductases of denitrifying bacteria and by the inducible NO synthases of immune cells of the host, respectively. The response of both microorganisms to NO was analyzed by using a two-dimensional gel approach. Metabolic labeling of the proteins revealed major changes in the synthesis pattern of cytosolic proteins after the addition of the NO donor MAHMA NONOate. Whereas B. subtilis induced several oxidative stress-responsive regulons controlled by Fur, PerR, OhrR, and Spx, as well as the general stress response controlled by the alternative sigma factor SigB, the more resistant S. aureus showed an increased synthesis rate of proteins involved in anaerobic metabolism. These data were confirmed by nuclear magnetic resonance analyses indicating that NO causes a drastically higher increase in the formation of lactate and butanediol in S. aureus than in B. subtilis. Monitoring the intracellular protein thiol state, we observed no increase in reversible or irreversible protein thiol modifications after NO stress in either organism. Obviously, NO itself does not cause general protein thiol oxidations. In contrast, exposure of cells to NO prior to peroxide stress diminished the irreversible thiol oxidation caused by hydrogen peroxide.Bacillus subtilis and Staphylococcus aureus are gram-positive model bacteria. Whereas B. subtilis is considered to be harmless, S. aureus is a facultative pathogen and the leading cause of nosocomial and community-acquired infections. Both microorganisms have to cope with high amounts of nitric oxide (NO) (up to the M range) generated from coexisting denitrifying bacteria or from the innate immune response of the host, respectively (17,31,55,68). Hence, the ability of B. subtilis and S. aureus to protect themselves against NO might be crucial for survival in their respective natural habitats.The cytotoxic properties of the small, lipophilic, and freely diffusible radical NO are attributed to its high reactivity. Indirect effects of NO are caused by the reaction of the radical with oxygen or superoxide, resulting in the formation of a number of additional reactive nitrogen species, including nitrogen dioxide, peroxynitrite, and dinitrogen trioxide. These nitrogen species differ in reactivity, stability, and biological activity but result in a broad spectrum of antimicrobial activity (25). In general, reactive oxygen and nitrogen species can interact with numerous targets, including thiols, metal centers, tyrosine residues in proteins, nucleotide bases, and lipids (20,69). NO directly affects the activity of enzymes by the reaction with bound free radicals or with metal centers (51, 72, 100). For example, the formation of metal-nitrosyl complexes in respiratory enzymes was shown to inhibit bacterial respiration (8,13,71,88) and the formation of a dinitrosyl-iron complex of a protein essential for branched-chain am...

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Section: Vol 190 2008 Nitric Oxide Stress In B Subtilis and S Aurmentioning

confidence: 57%

Nitric Oxide Stress Induces Different Responses but Mediates Comparable Protein Thiol Protection inBacillus subtilisandStaphylococcus aureus

et al. 2008

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“…2.8-fold in rd10, RCL vs. Table 3; Column 3) or no statistical difference was found in our dataset (wild type and rd10 retinas, RCL-L vs. RCL-D, Columns 1,2 and 4 in Table 3). High levels of nitric oxide (NO) are indicative of nitrosative stress (Thomas et al, 2006) that, along with oxidative stress, is known to inactivate enzymes, modify DNA to form 8-oxo and 8-nitroguanine, as well as generate lipid hydroperoxides and other modified lipids (Aicardo et al, 2016;Liu et al, 2002). In contrast to nitrosoproline, nitrotyrosine exhibited fewer differences between rd10 and wild type retinas.…”

Section: Resultsmentioning

confidence: 99%

Broad spectrum metabolomics for detection of abnormal metabolic pathways in a mouse model for retinitis pigmentosa

Weiss

Osawa

Xiong

et al. 2019

Experimental Eye Research

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Retinitis pigmentosa (RP) is a degenerative disease of the retina that affects approximately 1 million people worldwide. There are multiple genetic causes of this disease, for which, at present, there are no effective therapeutic strategies. In the present report, we utilized broad spectrum metabolomics to identify perturbations in the metabolism of the rd10 mouse, a genetic model for RP that contains a mutation in Pde6β. These data provide novel insights into mechanisms that are potentially critical for retinal degeneration. C57BL/6J and rd10 mice were raised in cyclic light followed by either light or dark adaptation at postnatal day (P) 18, an early stage in the degeneration process. Mice raised entirely in the dark until P18 were also evaluated. After euthanasia, retinas were removed and extracted for analysis by ultra-performance liquid chromatography-time of flight-mass spectrometry (UPLC-QTOF-MS). Compared to wild type mice, rd10 mice raised in cyclic light or in complete darkness demonstrate significant alterations in retinal pyrimidine and purine nucleotide metabolism, potentially disrupting deoxynucleotide pools necessary for mitochondrial DNA replication. Other metabolites that demonstrate significant increases are the Coenzyme A intermediate, 4'-phosphopantothenate, and acylcarnitines. The

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“…In matrix metalloproteases (MMPs), sulfinic acid oxidation of a zinc-coordinated active site cysteine thiolate activates protease function, in part by reducing the ability to coordinate the zinc cation. 211 In contrast, nonheme Fe III coordination in nitrile hydratases (NHases) is accomplished by a unique CXXCXC binding sequence in which two cysteines are present as the sulfinic and sulfenic acid states. 154 , 212 Cysteine oxidation is necessary for hydratase activity, and the increased Lewis acidity of the Fe III afforded by cysteine oxidation is believed to regulate the affinity of a catalytic water molecule for the metal center.…”

Section: Reactive Oxygen Species (Ros) In Biological Systemsmentioning

confidence: 99%

Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery

2013

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The Chemistry of Protein Modifications Elicited by Nitric Oxide and Related Nitrogen Oxides

Cited by 8 publications

References 145 publications

Nitric Oxide Stress Induces Different Responses but Mediates Comparable Protein Thiol Protection inBacillus subtilisandStaphylococcus aureus

Nitric Oxide Stress Induces Different Responses but Mediates Comparable Protein Thiol Protection inBacillus subtilisandStaphylococcus aureus

Broad spectrum metabolomics for detection of abnormal metabolic pathways in a mouse model for retinitis pigmentosa

Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery

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