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The chemical biology of nitric oxide: implications in cellular signaling.

Publication ,  Journal Article
Thomas, DD; Ridnour, LA; Isenberg, JS; Flores-Santana, W; Switzer, CH; Donzelli, S; Hussain, P; Vecoli, C; Paolocci, N; Ambs, S; Colton, CA ...
Published in: Free Radic Biol Med
July 1, 2008

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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Published In

Free Radic Biol Med

DOI

ISSN

0891-5849

Publication Date

July 1, 2008

Volume

45

Issue

1

Start / End Page

18 / 31

Location

United States

Related Subject Headings

  • Signal Transduction
  • Nitric Oxide
  • Kinetics
  • Humans
  • Diffusion
  • Biochemistry & Molecular Biology
  • Animals
  • 3205 Medical biochemistry and metabolomics
  • 3101 Biochemistry and cell biology
  • 1101 Medical Biochemistry and Metabolomics
 

Citation

APA
Chicago
ICMJE
MLA
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Thomas, D. D., Ridnour, L. A., Isenberg, J. S., Flores-Santana, W., Switzer, C. H., Donzelli, S., … Wink, D. A. (2008). The chemical biology of nitric oxide: implications in cellular signaling. Free Radic Biol Med, 45(1), 18–31. https://doi.org/10.1016/j.freeradbiomed.2008.03.020
Thomas, Douglas D., Lisa A. Ridnour, Jeffrey S. Isenberg, Wilmarie Flores-Santana, Christopher H. Switzer, Sonia Donzelli, Perwez Hussain, et al. “The chemical biology of nitric oxide: implications in cellular signaling.Free Radic Biol Med 45, no. 1 (July 1, 2008): 18–31. https://doi.org/10.1016/j.freeradbiomed.2008.03.020.
Thomas DD, Ridnour LA, Isenberg JS, Flores-Santana W, Switzer CH, Donzelli S, et al. The chemical biology of nitric oxide: implications in cellular signaling. Free Radic Biol Med. 2008 Jul 1;45(1):18–31.
Thomas, Douglas D., et al. “The chemical biology of nitric oxide: implications in cellular signaling.Free Radic Biol Med, vol. 45, no. 1, July 2008, pp. 18–31. Pubmed, doi:10.1016/j.freeradbiomed.2008.03.020.
Thomas DD, Ridnour LA, Isenberg JS, Flores-Santana W, Switzer CH, Donzelli S, Hussain P, Vecoli C, Paolocci N, Ambs S, Colton CA, Harris CC, Roberts DD, Wink DA. The chemical biology of nitric oxide: implications in cellular signaling. Free Radic Biol Med. 2008 Jul 1;45(1):18–31.
Journal cover image

Published In

Free Radic Biol Med

DOI

ISSN

0891-5849

Publication Date

July 1, 2008

Volume

45

Issue

1

Start / End Page

18 / 31

Location

United States

Related Subject Headings

  • Signal Transduction
  • Nitric Oxide
  • Kinetics
  • Humans
  • Diffusion
  • Biochemistry & Molecular Biology
  • Animals
  • 3205 Medical biochemistry and metabolomics
  • 3101 Biochemistry and cell biology
  • 1101 Medical Biochemistry and Metabolomics