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Cited by 310Nitric Oxide and Endothelin EffectsRedox biology and oxidative stressHemoglobin structure and function

What Part of NO Don't You Understand? Some Answers to the Cardinal Questions in Nitric Oxide Biology

Open access
Hill, Bradford G., Dranka, Brian P., Bailey, Shannon M., Lancaster, Jack R., Darley-Usmar, Victor M.·2010·Journal of Biological Chemistry
DOI 10.1074/jbc.r110.101618PMC PMC2888379
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Abstract

Nitric oxide (NO) regulates biological processes through signaling mechanisms that exploit its unique biochemical properties as a free radical. For the last several decades, the key aspects of the chemical properties of NO relevant to biological systems have been defined, but it has been a challenge to assign these to specific cellular processes. Nevertheless, it is now clear that the high affinity of NO for transition metal centers, particularly iron, and the rapid reaction of NO with oxygen-derived free radicals can explain many of its biological and pathological properties. Emerging studies also highlight a growing importance of the secondary metabolites of NO-dependent reactions in the post-translational modification of key metabolic and signaling proteins. In this minireview, we emphasize the current understanding of the biochemistry of NO and place it in a biological context.

AI snapshot

Written from the paper’s full text.

TL;DR

This minireview explains nitric oxide (NO) biology through its free-radical chemistry, especially high-affinity binding to iron/transition metals and rapid reaction with superoxide to form peroxynitrite. It proposes a concentration- and location-dependent “bullseye” model of NO targets and highlights unresolved issues in NO signaling, nitrite reduction, and NO-dependent protein modifications.

Key findings

  • NO’s direct biological reactivity is limited; key actions involve high-affinity binding to ferrous heme/iron proteins such as sGC, CcOx, and NHI, and rapid reaction with superoxide to form peroxynitrite, with a reported rate constant as high as 1.9 × 10^10 M^-1 s^-1, near the diffusion limit.
  • The proposed “bullseye” model ranks target sensitivity as sGC most sensitive, followed by CcOx and then NHI; when ROS such as superoxide are present, NO must exceed superoxide levels to activate sGC, and oxidative/nitrative modifications of proteins, lipids, and DNA become more prominent.
  • NO half-lives are reported in the range of 2 ms to >2 s depending on intracellular reactants; peroxynitrite reacts with free cysteine at 5.9 × 10^3 M^-1 s^-1 but much more slowly with protein thiols, which may contribute to target selectivity.
  • S-nitrosation can occur by four mechanisms—radical-radical reaction, transnitrosation, N2O3, and transfer from metal nitrosyls—and well over 100 proteins have been reported S-nitrosated; nitrite can be reduced back to NO by heme proteins under hypoxia, though its physiological role remains debated.

Methods

  • Narrative minireview with no primary experimental data; it synthesizes literature on NO formation, chemistry, metalloprotein targets, reactive nitrogen species, and pathophysiological examples from hepatology and cardiovascular biology.
  • The authors note a PubMed keyword search for “nitric oxide” returns over 99,000 references, so they selectively cite predominantly review articles; the paper includes Table 1 of nitrogen species/adducts and Figure 1 as a conceptual bullseye model.
  • Main analysis is conceptual integration of NO biochemistry with biological effects; no systematic review, meta-analysis, or statistical analysis is reported.

Limitations

  • Stated by the paper: a comprehensive review is not feasible; controversy remains about biologically achievable NO levels; mechanisms of in vivo nitrite formation are elusive; relative contributions of S-nitrosation mechanisms are unclear; there is no general consensus on NO-hemoglobin interactions; and whether nitrite reduction to NO is physiological remains to be seen.
  • Evident from the text: this is a selective narrative review with predominantly review citations, no systematic search or quantitative synthesis, and no primary data to validate the proposed bullseye model; several areas are described as speculative or contentious.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1074/jbc.r110.101618

Cites

70 of 70 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 122 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    NO and related nitrogen oxides are critical endogenous regulators of cell and tissue function.

    “Nitric oxide (NO; nitrogen monoxide) and related nitrogen oxides are now known to be critical endogenous regulators of cell and tissue function (1, 2).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [1] Moncada, 1991, Pharmacol. Rev. source

      Not checked in the free run.

    • cites [2] Pacher, 2007, Physiol. Rev. source

      Not checked in the free run.

  • Premisenone given

    Secondary metabolites of NO-dependent reactions are increasingly important in the post-translational modification of key metabolic and signaling proteins.

    “Emerging studies also highlight a growing importance of the secondary metabolites of NO-dependent reactions in the post-translational modification of key metabolic and signaling proteins.”
    Quote in the paperNot a substantial claim
  • Premisereasoning

    NO can stabilize its unpaired electron by reaction with species containing other unpaired electrons.

    “NO is a free radical and can stabilize its unpaired electron by two mechanisms: reaction with species containing other unpaired electrons (thus pairing up the two lone electrons) and interaction with the d-orbitals of transition metals, particularly iron.”
    Quote in the paperNot a substantial claim
  • Interpretationnone given

    Nitric oxide regulates biological processes through signaling mechanisms that exploit its unique biochemical properties as a free radical.

    “Nitric oxide (NO) regulates biological processes through signaling mechanisms that exploit its unique biochemical properties as a free radical.”
    Quote in the paperSubstantial claim
  • Premisenone given

    NO is a free radical.

    “NO is a free radical and can stabilize its unpaired electron by two mechanisms: reaction with species containing other unpaired electrons (thus pairing up the two lone electrons) and interaction with the d-orbitals of transition metals, particularly iron.”
    Quote in the paperSubstantial claim
  • May combine two claims. 28
  • Classified as probably not a substantial claim. 7

  • May combine two claims.

    Interpretationnone given

    The high affinity of NO for transition metal centers, particularly iron, and the rapid reaction of NO with oxygen-derived free radicals can explain many of its biological and pathological properties.

    “Nevertheless, it is now clear that the high affinity of NO for transition metal centers, particularly iron, and the rapid reaction of NO with oxygen-derived free radicals can explain many of its biological and pathological properties.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    NO binding to NHI can result in significant biological effects, including binding to the chelatable iron pool of cells.

    “NO binding to NHI can also result in significant biological effects, including disruption of iron-sulfur centers and also binding to the so-called chelatable iron pool of cells (17).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Butler, 2002, Chem. Rev. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Neuronal NOS is a Ca2+/calmodulin-dependent isoform that, in the brain, is activated physiologically by agonists of the N-methyl-d-aspartate receptor.

    “It is also a Ca2+/calmodulin-dependent isoform that, in the brain, is activated physiologically by agonists of the N-methyl-d-aspartate receptor (27).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Kone, 2003, Am. J. Physiol. Renal Physiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Once NO has reacted with O2 ̇̄, it forms peroxynitrite and no longer participates in signaling actions that require binding to ferrous heme.

    “Once it has reacted with O2˙̄, it forms peroxynitrite and no longer participates in those signaling actions, which require binding to ferrous heme (23).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] McAndrew, 1997, Semin. Perinatol. source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    NO is chemically stable and much less reactive with non-radical species than the hydroxyl radical but more reactive than lipid peroxyl radicals.

    “To place this in perspective, NO is chemically stable and much less reactive with non-radical species than the hydroxyl radical but more reactive than lipid peroxyl radicals.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Three distinct NOS isoforms have been identified, all of which have different characteristics and generate NO at different rates.

    “Three distinct isoforms have been identified, all of which have different characteristics and generate NO at different rates (27).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Kone, 2003, Am. J. Physiol. Renal Physiol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Neuronal NOS (NOS1) is constitutively present in neurons, skeletal muscle, and epithelial cells.

    “Neuronal NOS (NOS1) is constitutively present in neurons, skeletal muscle, and epithelial cells.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    NO is uncharged and highly soluble in hydrophobic environments.

    “NO is uncharged and highly soluble in hydrophobic environments.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    eNOS was originally discovered in the vascular endothelium but is also found in neurons, epithelial cells, and cardiac myocytes.

    “eNOS (NOS3) generates the lowest levels of NO and was originally discovered in the vascular endothelium but is also found in neurons, epithelial cells, and cardiac myocytes (28).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Dudzinski, 2007, Cardiovasc. Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NOS enzymes are regulated by post-translational modifications, controlled localization within the cell, substrate and cofactor availability, and other proteins with which they form stable complexes.

    “The NOS enzymes are regulated by post-translational modifications, controlled localization within the cell, substrate and cofactor availability, and other proteins with which they form stable complexes (27).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Kone, 2003, Am. J. Physiol. Renal Physiol. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Since the realization that peroxynitrite is produced in biological systems, it has been proposed to be a major mediator of the pathological effects associated with NO, particularly inflammation.

    “Since the realization that peroxynitrite is produced in biological systems, it has been proposed to be a major mediator of the pathological effects associated with NO, particularly inflammation (22).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Beckman, 2009, Arch. Biochem. Biophys. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Reaction of NO with O2 in the biological milieu is almost certainly not important as a source of nitrite formation compared with other much more rapid mechanisms.

    “As we have speculated previously (41), reaction with O2 in the biological milieu is almost certainly not important as a source of nitrite formation compared with other much more rapid mechanisms (although it could conceivably be a localized source for reactive oxidative/nitrosative species, especially in hydrophobic environments).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Möller, 2007, IUBMB Life source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The regeneration of NO from nitrite changes the location of NO formation and decreases the dependence on oxygen.

    “The regeneration of NO from one of its metabolites would seem at first glance to be a futile exercise; however, this reaction both changes the location of NO formation and decreases the dependence on oxygen (35, 38).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [35] Lundberg, 2009, Nat. Chem. Biol. source

      Not checked in the free run.

    • cites [38] Lundberg, 2008, Nat. Rev. Drug Discov. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Nitrite (NO2−) can be reduced back to NO by heme proteins such as hemoglobin.

    “Recently, it has been suggested that a major metabolite of NO, nitrite (NO2−), can be reduced back to NO by heme proteins such as hemoglobin (35).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Lundberg, 2009, Nat. Chem. Biol. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Augmenting the rate of formation of NO increases the distance over which NO diffuses, which also increases the target (bullseye) size.

    “In addition, augmenting the rate of formation of NO increases the distance over which NO diffuses, which also increases the target (bullseye) size.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    As the concentration of NO increases, modification of NHI occurs, which can also regulate cell signaling.

    “As the concentration of NO increases, modification of NHI occurs, which can also regulate cell signaling (44).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Demple, 2002, Mol. Cell. Biochem. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Inducible NOS has been shown to be constitutively present in some tissues such as lung epithelium.

    “It has also been shown to be constitutively present in some tissues such as lung epithelium.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Several studies have suggested that mitochondrially localized or associated forms of NOS may play a specific role in the regulation of mitochondrial function.

    “For example, several studies have suggested that mitochondrially localized or associated forms of NOS may play a specific role in the regulation of mitochondrial function (33, 34).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [33] Finocchietto, 2009, Exp. Biol. Med. source

      Not checked in the free run.

    • cites [34] Kato, 2006, Front. Biosci. source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Peroxynitrite reacts directly with sulfur-containing amino acids (cysteine and methionine), as well as those with aromatic structure (e.g. tryptophan and tyrosine).

    “Peroxynitrite reacts directly with sulfur-containing amino acids (cysteine and methionine), as well as those with aromatic structure (e.g. tryptophan and tyrosine).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Both alcoholic steatohepatitis and nonalcoholic steatohepatitis are associated with increased hypoxia.

    “Recently, we have shown that both alcoholic steatohepatitis and nonalcoholic steatohepatitis are associated with increased sensitivity of the respiratory chain to inhibition by NO, increased hypoxia, and protein nitration (54, 68, 69).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [54] Shiva, 2005, Free Radic. Biol. Med. source

      Not checked in the free run.

    • cites [68] Venkatraman, 2004, Hepatology source

      Not checked in the free run.

    • cites [69] Mantena, 2009, Biochem. J. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    sGC does not bind O2 but forms 5-coordinate Fe2+·NO complexes that activate the enzyme and are responsible for the cGMP-dependent effects of NO.

    “For instance, sGC does not bind O2 but does form 5-coordinate Fe2+·NO complexes, which subsequently activate the enzyme and are responsible for the cGMP-dependent effects of NO.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [14] Garthwaite, 2010, Mol. Cell. Biochem. source

      Not checked in the free run.

    • cites [15] Derbyshire, 2009, Handb. Exp. Pharmacol.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both alcoholic steatohepatitis and nonalcoholic steatohepatitis are associated with increased sensitivity of the respiratory chain to inhibition by NO.

    “Recently, we have shown that both alcoholic steatohepatitis and nonalcoholic steatohepatitis are associated with increased sensitivity of the respiratory chain to inhibition by NO, increased hypoxia, and protein nitration (54, 68, 69).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [54] Shiva, 2005, Free Radic. Biol. Med. source

      Not checked in the free run.

    • cites [68] Venkatraman, 2004, Hepatology source

      Not checked in the free run.

    • cites [69] Mantena, 2009, Biochem. J. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NO may be generated within the red blood cell by metabolism of nitrite or through the presence of an erythrocytic NOS.

    “NO may be generated within the red blood cell by metabolism of nitrite or, intriguingly, through the presence of an erythrocytic NOS (57).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Ozüyaman, 2008, Trends Mol. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both alcoholic steatohepatitis and nonalcoholic steatohepatitis are associated with protein nitration.

    “Recently, we have shown that both alcoholic steatohepatitis and nonalcoholic steatohepatitis are associated with increased sensitivity of the respiratory chain to inhibition by NO, increased hypoxia, and protein nitration (54, 68, 69).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [54] Shiva, 2005, Free Radic. Biol. Med. source

      Not checked in the free run.

    • cites [68] Venkatraman, 2004, Hepatology source

      Not checked in the free run.

    • cites [69] Mantena, 2009, Biochem. J. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    If nitration were solely dependent on NO2 ̇, this mechanism would require two molecules of the oxidant and is therefore less likely to occur biologically.

    “If solely dependent on NO2˙, this mechanism would require two molecules of the oxidant and is therefore less likely to occur biologically.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Proteins may be S-nitrosated by N2O3, which is formed from the reaction of NO with O2.

    “3) Proteins may also be S-nitrosated by N2O3, which is formed from the reaction of NO with O2.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Zhang, 2005, Free Radic. Biol. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Nitration could be mediated by nitrogen dioxide (NO2 ̇), which is an important environmental toxin and a byproduct of the reaction of NO with O2.

    “In addition, nitration could be mediated by nitrogen dioxide (NO2˙), which is an important environmental toxin and a byproduct of the reaction of NO with O2.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    NO regulates mitochondrial function through reversible binding at the heme site in CcOx, which inhibits O2 consumption and can influence cross-talk mechanisms between the mitochondrion and sGC.

    “As discussed above, NO regulates mitochondrial function through reversible binding at the heme site in CcOx, which inhibits O2 consumption and can influence cross-talk mechanisms between the mitochondrion and sGC.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Hemoglobin and CcOx have different affinities for NO but also bind O2.

    “In contrast, hemoglobin and CcOx have different affinities for NO but also bind O2 (15).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Derbyshire, 2009, Handb. Exp. Pharmacol.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The extremely rapid reaction of NO with HbO2 converts NO to nitrate, and NO binds very rapidly to deoxyheme to form a stable complex.

    “The extremely rapid reaction with HbO2 results in conversion of the NO to nitrate, and NO binds very rapidly to the deoxyheme to form a stable complex (35, 36).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [35] Lundberg, 2009, Nat. Chem. Biol. source

      Not checked in the free run.

    • cites [36] Gladwin, 2009, Acc. Chem. Res. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    These biochemical mechanisms can operate simultaneously within the context of any specific organ or cell.

    “It is now becoming clear that these biochemical mechanisms can operate simultaneously within the context of any specific organ or cell.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    These NO-dependent changes lead to bioenergetic dysfunction, reductive stress, and ROS production, which are key features of mitochondrial dysfunction in diabetes/obesity and alcohol-mediated liver disease.

    “This leads to bioenergetic dysfunction, reductive stress, and ROS production, all of which are key features of mitochondrial dysfunction in diabetes/obesity and alcohol-mediated liver disease.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    A consequence of this inhibition would be to extend the O2 gradient within tissues and prevent hypoxia.

    “A consequence of this inhibition would be to extend the O2 gradient within tissues and prevent hypoxia.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The protective effects of NO, like its deleterious actions, involve its binding to ferrous iron and its regulation of protein thiol modifications.

    “These findings suggest that, like its deleterious actions, the protective effects of NO also involve its binding to ferrous iron and its regulation of protein thiol modifications.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    A cardioprotective mitochondrially targeted S-nitrosothiol was shown recently to enhance oxygen levels under hypoxic conditions and to promote S-nitrosation of mitochondrial protein thiols.

    “Indeed, a cardioprotective mitochondrially targeted S-nitrosothiol was shown recently to enhance oxygen levels under hypoxic conditions and to promote S-nitrosation of mitochondrial protein thiols (63).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [63] Bosworth, 2009, Proc. Natl. Acad. Sci. U.S.A. source

      Not checked in the free run.

35 of 35

  • The paper relies on this without support.

    Mitochondrial dysfunction and altered NO bioavailability, down-regulation of the sGC pathway, and increased protein modifications play a key role in the pathogenesis of liver disease.

    “Importantly, mitochondrial dysfunction and altered NO bioavailability, down-regulation of the sGC pathway, and increased protein modifications play a key role in the pathogenesis of liver disease.”

  • The paper relies on this without support.

    NO reacts with metalloproteins by nitrosylating ferrous iron (Fe2+).

    “The reaction of NO with metalloproteins involves nitrosylation of ferrous iron (Fe2+).”

  • The paper relies on this without support.

    Ligand discrimination between metalloproteins differs widely because of the effects of the protein structure.

    “However, ligand discrimination between metalloproteins differs widely because of the effects of the protein structure.”

  • The paper relies on this without support.

    Interaction of NO with hemoglobin or myoglobin typically results in its consumption.

    “Unlike CcOx, interaction of NO with hemoglobin or myoglobin typically results in its consumption.”

  • The paper relies on this without support.

    Several proteins have cysteines that react with RNS and are nitrosated, glutathiolated, and/or oxidized.

    “Several proteins have cysteines that react with RNS and are nitrosated, glutathiolated, and/or oxidized.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Low NO levels (pM/nM) are physiological and related to activation of high-affinity primary binding targets such as soluble guanylyl cyclase and cytochrome c oxidase.

    “It has been shown that low levels (pM/nM) are physiological and related to the activation of high affinity primary binding targets such as soluble guanylyl cyclase (sGC) and cytochrome c oxidase”

    From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [433]

  • The most common route of NO production is through the action of the nitric oxide synthase family of enzymes.

    “The most common route of NO production is through the action of the nitric oxide synthase (NOS) family of enzymes [62, 64].”

    From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [62]

  • The three isoforms of NOS generate NO at different rates.

    “The three isoforms of NOS generate NO at different rates [62].”

    From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [62]

  • Nitric oxide and related nitrogen oxides have emerged as critical regulators of cell and tissue function.

    “Nitric oxide and related nitrogen oxides have emerged as critical regulators of cell and tissue function [62].”

    From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [62]

  • Peroxynitrite and reactive species derived from it are important in inflammatory responses and can modulate cell signaling, in part by promoting oxidation or nitration of biomolecules.

    “Peroxynitrite and reactive species derived from it (e.g., nitrogen dioxide) are important in inflammatory responses [85] and can modulate cell signaling [87-90], in part by promoting the oxidation or nitration of a broad range of biomolecules [62].”

    From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [62]

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Derbyshire, 2009, Handb. Exp. Pharmacol., 191, 7

Cited by

Sorted by citations

Authors
Hill, B. G., Dranka, B. P., Bailey, S. M., Lancaster, J. R., & Darley-Usmar, V. M.
Affiliations
University of Alabama at Birmingham (US)
Corresponding author
Darley-Usmar, Victor M.
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2010-06
Volume
285
Issue
26
Pages
19699-19704
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.r110.101618
PMC
PMC2888379
OpenAlex
W2076736326
Semantic Scholar
42c8b44e215b8268664c2911d2384e80adbe54f5
Cited by
310
References
70
Citations by year
2026: 3 · 2025: 2 · 2024: 6 · 2023: 7 · 2022: 18 · 2021: 13 · 2020: 12 · 2019: 14 · 2018: 17 · 2017: 23 · 2016: 27 · 2015: 30 · 2014: 36 · 2013: 31 · 2012: 32
FWCI
3.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Institute on Alcohol Abuse and Alcoholism (R01AA018841, AA15172, R01AA013395, R01AA015172, AA-18841, AA-13395)
  • National Heart, Lung, and Blood Institute (F32HL010167, T32HL007918, T32-HL-07457, T32HL007457)
  • National Cancer Institute (CA-131653, R01CA131653)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R21DK073775, R01DK075865, R56DK075865, DK75865, DK73775)
  • National Institute of Environmental Health Sciences (ES/HL10167)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
Keywords
nitric oxide, no-signaling, free radicals, transition metal binding, iron, oxygen free radicals, post-translational modification, protein modification
MeSH terms
Animals, Cardiovascular System, Free Radicals, Hemoglobins, Humans, Iron, Nitric Oxide, Protein Binding, Protein Processing, Post-Translational, Signal Transduction

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