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Proc Natl Acad Sci U S A. 2018 Jun 5;115(23):5839-5848. doi: 10.1073/pnas.1804932115. Epub 2018 May 25.

Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine.

Radi R1,2.

Author information

1
Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, 11800 Montevideo, Uruguay; rradi@fmed.edu.uy.
2
Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, 11800 Montevideo, Uruguay.

Abstract

Oxygen-derived free radicals and related oxidants are ubiquitous and short-lived intermediates formed in aerobic organisms throughout life. These reactive species participate in redox reactions leading to oxidative modifications in biomolecules, among which proteins and lipids are preferential targets. Despite a broad array of enzymatic and nonenzymatic antioxidant systems in mammalian cells and microbes, excess oxidant formation causes accumulation of new products that may compromise cell function and structure leading to cell degeneration and death. Oxidative events are associated with pathological conditions and the process of normal aging. Notably, physiological levels of oxidants also modulate cellular functions via homeostatic redox-sensitive cell signaling cascades. On the other hand, nitric oxide (NO), a free radical and weak oxidant, represents a master physiological regulator via reversible interactions with heme proteins. The bioavailability and actions of NO are modulated by its fast reaction with superoxide radical ([Formula: see text]), which yields an unusual and reactive peroxide, peroxynitrite, representing the merging of the oxygen radicals and NO pathways. In this Inaugural Article, I summarize early and remarkable developments in free radical biochemistry and the later evolution of the field toward molecular medicine; this transition includes our contributions disclosing the relationship of NO with redox intermediates and metabolism. The biochemical characterization, identification, and quantitation of peroxynitrite and its role in disease processes have concentrated much of our attention. Being a mediator of protein oxidation and nitration, lipid peroxidation, mitochondrial dysfunction, and cell death, peroxynitrite represents both a pathophysiologically relevant endogenous cytotoxin and a cytotoxic effector against invading pathogens.

KEYWORDS:

free radicals; nitric oxide; oxidation; peroxynitrite; protein tyrosine nitration

PMID:
29802228
DOI:
10.1073/pnas.1804932115
[Indexed for MEDLINE]
Free PMC Article

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