Related Experiment Video
Updated: Aug 14, 2026

Detection of Nitric Oxide and Superoxide Radical Anion by Electron Paramagnetic Resonance Spectroscopy from Cells using Spin Traps
Published on: August 18, 2012
Mechanisms of cell death governed by the balance between nitrosative and oxidative stress
M G Espey1, K M Miranda, M Feelisch
1Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. SP@nih.gov
Abstract:
Many cellular functions in physiology are regulated by the direct interaction of NO with target biomolecules. In many pathophysiologic and toxicologic mechanisms, NO first reacts with oxygen, superoxide or other nitrogen oxides to subsequently elicit indirect effects. The balance between nitrosative stress and oxidative stress within a specific biological compartment can determine whether the presence of NO will be ultimately deleterious or beneficial. Nitrosative stress can be defined primarily through reactions mediated by N2O3, a reactive nitrogen oxide species generated by high fluxes of NO in an aerobic environment. In contrast, oxidative stress is mediated primarily by superoxide and peroxides. In addition to reactive oxygen species, several reactive nitrogen oxide species such as peroxynitrite, nitroxyl, and nitrogen dioxide can also impose oxidative stress to a cell. We here describe how the mechanisms of cell death are interwoven in the balance between the different chemical intermediates involved in nitrosative and oxidative stress.
Insights
Nitric oxide (NO) interactions with biomolecules are key to cell function. The balance between nitrosative stress and oxidative stress, influenced by NO reactions, determines cell fate, impacting cellular functions and survival.
Area of Science:
- Biochemistry
- Cell Biology
- Toxicology
Background:
- Cellular functions are regulated by nitric oxide (NO) interacting with biomolecules.
- Pathophysiology and toxicology involve indirect effects of NO through reactions with oxygen and nitrogen oxides.
- The balance between nitrosative and oxidative stress dictates NO's beneficial or detrimental role.
Purpose of the Study:
- To elucidate the mechanisms of cell death.
- To explore the interplay between nitrosative and oxidative stress.
- To define the role of reactive nitrogen oxide species (RNOS) in cellular stress.
Main Methods:
- Analysis of NO reactions with oxygen, superoxide, and other nitrogen oxides.
- Characterization of reactive nitrogen oxide species (RNOS) like N2O3, peroxynitrite, nitroxyl, and nitrogen dioxide.
- Investigation of cellular stress pathways.
Main Results:
- Nitrosative stress is primarily mediated by N2O3, formed from high NO fluxes in aerobic conditions.
- Oxidative stress is mainly caused by superoxide and peroxides.
- Various RNOS, including peroxynitrite, nitroxyl, and nitrogen dioxide, contribute to oxidative stress.
Conclusions:
- Cell death mechanisms are intricately linked to the chemical intermediates of nitrosative and oxidative stress.
- Understanding the balance between these stresses is crucial for comprehending cellular responses.
- RNOS play a significant role in mediating cellular damage and death.
Related Concept Videos
Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
Cellular Injury I: Introduction
Cellular Injury IlI: Cellular Death
Cellular Injury IV: Necrosis
Cellular Injury V: Apoptosis and Autophagy

