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Cited by 977Nitric Oxide and Endothelin EffectsRedox biology and oxidative stressHemoglobin structure and function

The DOI matches its Crossref record; 159 of the 166 references it cites were found in a registry or an index.

The chemical biology of nitric oxide: Implications in cellular signaling

Open access
Thomas, Douglas D., Ridnour, Lisa A., Isenberg, Jeffrey S., Flores-Santana, Wilmarie, Switzer, Christopher H., Donzelli, Sonia, Hussain, Perwez, Vecoli, Cecilia, Paolocci, Nazareno, Ambs, Stefan, Colton, Carol A., Harris, Curtis C., Roberts, David D., Wink, David A.·2008·Free Radical Biology and Medicine
DOI 10.1016/j.freeradbiomed.2008.03.020PMC PMC2572721
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Abstract

Nitric oxide (NO) has earned the reputation of being a signaling mediator with many diverse and often opposing biological activities. The diversity in response to this simple diatomic molecule comes from the enormous variety of chemical reactions and biological properties associated with it. In the past few years, the importance of steady-state NO concentrations has emerged as a key determinant of its biological function. Precise cellular responses are differentially regulated by specific NO concentration. We propose five basic distinct concentration levels of NO activity: cGMP-mediated processes ([NO]<1-30 nM), Akt phosphorylation ([NO] = 30-100 nM), stabilization of HIF-1alpha ([NO] = 100-300 nM), phosphorylation of p53 ([NO]>400 nM), and nitrosative stress (1 microM). In general, lower NO concentrations promote cell survival and proliferation, whereas higher levels favor cell cycle arrest, apoptosis, and senescence. Free radical interactions will also influence NO signaling. One of the consequences of reactive oxygen species generation is to reduce NO concentrations. This antagonizes the signaling of nitric oxide and in some cases results in converting a cell-cycle arrest profile to a cell survival profile. The resulting reactive nitrogen species that are generated from these reactions can also have biological effects and increase oxidative and nitrosative stress responses. A number of factors determine the formation of NO and its concentration, such as diffusion, consumption, and substrate availability, which are referred to as kinetic determinants for molecular target interactions. These are the chemical and biochemical parameters that shape cellular responses to NO. Herein we discuss signal transduction and the chemical biology of NO in terms of the direct and indirect reactions.

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Research works printed but not linked: 2

  1. Wink, 1998, Chemical biology of nitric oxide: insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide, Free Radic. Biol. Med., 25, 434, 10.1016/S0891-5849(98)00092-6 · DOI · Paper page
  2. Lymar, 1995, Rapid reaction between peroxynitrite ion and carbon dioxide: implications for biological activity, J. Am. Chem. Soc., 290, 52

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Metadata

Authors
Thomas, D. D., Ridnour, L. A., Isenberg, J. S., Flores-Santana, W., Switzer, C. H., Donzelli, S., Hussain, P., Vecoli, C., Paolocci, N., Ambs, S., Colton, C. A., Harris, C. C., Roberts, D. D., & Wink, D. A.
Affiliations
  • University of Illinois Chicago (US)
  • National Institutes of Health (US)
  • Johns Hopkins University (US)
  • Duke University (US)
Corresponding author
Wink, David A.
ORCID
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2008-07
Volume
45
Issue
1
Pages
18-31
ISSN
0891-5849 (ISSN-L)
DOI
10.1016/j.freeradbiomed.2008.03.020
PMC
PMC2572721
OpenAlex
W1980458823
Cited by
975
References
166
Citations by year
2026: 33 · 2025: 44 · 2024: 37 · 2023: 54 · 2022: 57 · 2021: 73 · 2020: 58 · 2019: 55 · 2018: 54 · 2017: 45 · 2016: 53 · 2015: 63 · 2014: 67 · 2013: 50 · 2012: 69
FWCI
5.87
Type
journal article
Language
en
Open access
Licence
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (K22CA113315, Z01BC010033)
Topics
  • Health Sciences › Medicine › Physiology (medical) › 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 › Biochemistry › Hemoglobin structure and function
Keywords
nitric oxide, signal transduction, NO concentration, cGMP signaling, Akt phosphorylation, HIF-1α stabilization, p53 phosphorylation, nitrosative stress, reactive oxygen species, reactive nitrogen species, oxidative stress, cell cycle arrest, apoptosis, senescence
MeSH terms
Animals, Diffusion, Humans, Kinetics, Nitric Oxide, Signal Transduction

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