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

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.

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