Signaling and stress: The redox landscape in NOS2 biology

Douglas D. Thomas, Julie L. Heinecke, Lisa A. Ridnour, Robert Y. Cheng, Aparna H. Kesarwala, Christopher H. Switzer, Daniel W. McVicar, David D. Roberts, Sharon Glynn, Jon M. Fukuto, David A. Wink, Katrina M Miranda

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Nitric oxide (NO) has a highly diverse range of biological functions from physiological signaling and maintenance of homeostasis to serving as an effector molecule in the immune system. However, deleterious as well as beneficial roles of NO have been reported. Many of the dichotomous effects of NO and derivative reactive nitrogen species (RNS) can be explained by invoking precise interactions with different targets as a result of concentration and temporal constraints. Endogenous concentrations of NO span five orders of magnitude, with levels near the high picomolar range typically occurring in short bursts as compared to sustained production of low micromolar levels of NO during immune response. This article provides an overview of the redox landscape as it relates to increasing NO concentrations, which incrementally govern physiological signaling, nitrosative signaling and nitrosative stress-related signaling. Physiological signaling by NO primarily occurs upon interaction with the heme protein soluble guanylyl cyclase. As NO concentrations rise, interactions with nonheme iron complexes as well as indirect modification of thiols can stimulate additional signaling processes. At the highest levels of NO, production of a broader range of RNS, which subsequently interact with more diverse targets, can lead to chemical stress. However, even under such conditions, there is evidence that stress-related signaling mechanisms are triggered to protect cells or even resolve the stress. This review therefore also addresses the fundamental reactions and kinetics that initiate signaling through NO-dependent pathways, including processes that lead to interconversion of RNS and interactions with molecular targets.

Original languageEnglish (US)
Article number12462
Pages (from-to)204-225
Number of pages22
JournalFree Radical Biology and Medicine
Volume87
DOIs
StatePublished - Jun 2 2015

Fingerprint

Oxidation-Reduction
Nitric Oxide
Reactive Nitrogen Species
Hemeproteins
Guanylate Cyclase
Immune system
Sulfhydryl Compounds
Immune System
Homeostasis
Iron
Maintenance
Derivatives
Molecules
Kinetics

Keywords

  • Breast cancer
  • Cancer biology
  • Cell signaling
  • Freeradicals
  • Nitric oxide
  • Nitric oxidesynthase

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Thomas, D. D., Heinecke, J. L., Ridnour, L. A., Cheng, R. Y., Kesarwala, A. H., Switzer, C. H., ... Miranda, K. M. (2015). Signaling and stress: The redox landscape in NOS2 biology. Free Radical Biology and Medicine, 87, 204-225. [12462]. https://doi.org/10.1016/j.freeradbiomed.2015.06.002

Signaling and stress : The redox landscape in NOS2 biology. / Thomas, Douglas D.; Heinecke, Julie L.; Ridnour, Lisa A.; Cheng, Robert Y.; Kesarwala, Aparna H.; Switzer, Christopher H.; McVicar, Daniel W.; Roberts, David D.; Glynn, Sharon; Fukuto, Jon M.; Wink, David A.; Miranda, Katrina M.

In: Free Radical Biology and Medicine, Vol. 87, 12462, 02.06.2015, p. 204-225.

Research output: Contribution to journalArticle

Thomas, DD, Heinecke, JL, Ridnour, LA, Cheng, RY, Kesarwala, AH, Switzer, CH, McVicar, DW, Roberts, DD, Glynn, S, Fukuto, JM, Wink, DA & Miranda, KM 2015, 'Signaling and stress: The redox landscape in NOS2 biology', Free Radical Biology and Medicine, vol. 87, 12462, pp. 204-225. https://doi.org/10.1016/j.freeradbiomed.2015.06.002
Thomas DD, Heinecke JL, Ridnour LA, Cheng RY, Kesarwala AH, Switzer CH et al. Signaling and stress: The redox landscape in NOS2 biology. Free Radical Biology and Medicine. 2015 Jun 2;87:204-225. 12462. https://doi.org/10.1016/j.freeradbiomed.2015.06.002
Thomas, Douglas D. ; Heinecke, Julie L. ; Ridnour, Lisa A. ; Cheng, Robert Y. ; Kesarwala, Aparna H. ; Switzer, Christopher H. ; McVicar, Daniel W. ; Roberts, David D. ; Glynn, Sharon ; Fukuto, Jon M. ; Wink, David A. ; Miranda, Katrina M. / Signaling and stress : The redox landscape in NOS2 biology. In: Free Radical Biology and Medicine. 2015 ; Vol. 87. pp. 204-225.
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