Cited by 1,726Redox biology and oxidative stressAntioxidant Activity and Oxidative StressSulfur Compounds in Biology

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Redefining Oxidative Stress

Jones, Dean P.·2006·Antioxidants & Redox Signaling

DOI 10.1089/ars.2006.8.1865

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Abstract

Oxidative stress is often defined as an imbalance of pro-oxidants and antioxidants, which can be quantified in humans as the redox state of plasma GSH/GSSG. Plasma GSH redox in humans becomes oxidized with age, in response to oxidative stress (chemotherapy, smoking), and in common diseases (type 2 diabetes, cardiovascular disease). However, data also show that redox of plasma GSH/GSSG is not equilibrated with the larger plasma cysteine/cystine (Cys/CySS) pool, indicating that the "balance" of pro-oxidants and antioxidants cannot be defined by a single entity. The major cellular thiol/disulfide systems, including GSH/GSSG, thioredoxin- 1 (-SH(2)/-SS-), and Cys/CySS, are not in redox equilibrium and respond differently to chemical toxicants and physiologic stimuli. Individual signaling and control events occur through discrete redox pathways rather than through mechanisms that are directly responsive to a global thiol/disulfide balance such as that conceptualized in the common definition of oxidative stress. Thus, from a mechanistic standpoint, oxidative stress may be better defined as a disruption of redox signaling and control. Adoption of such a definition could redirect research to identify key perturbations of redox signaling and control and lead to new treatments for oxidative stress-related disease processes.

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Self-citation

Authors: Jones, D. P.
Affiliations: Emory University (US)
Corresponding author: Jones, Dean P.
ORCID: Jones, Dean P.
Venue: Antioxidants & Redox Signaling
Publisher: SAGE Publications
Published: 2006-09
Volume: 8
Issue: 9-10
Pages: 1865-1879
ISSN: 1523-0864 (ISSN-L)
1557-7716
DOI: 10.1089/ars.2006.8.1865
OpenAlex: W1970240791
Semantic Scholar: 21aa29343a7c35ad93ce5d00685d8074eb1f4efa
Cited by: 1,726
References: 66
Citations by year: 2026: 94 · 2025: 51 · 2024: 84 · 2023: 92 · 2022: 96 · 2021: 109 · 2020: 97 · 2019: 87 · 2018: 100 · 2017: 87 · 2016: 105 · 2015: 90 · 2014: 109 · 2013: 89 · 2012: 109
FWCI: 4.16
Type: journal article
Language: en
Open access: closed
Locations: Antioxidants and Redox Signaling (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Environmental Health Sciences (R01ES009047, R01-ES-09047, R01ES011195)
National Center for Research Resources (M01-RR00039, M01RR000039)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
Keywords: oxidative stress, redox signaling, glutathione, glutathione disulfide, thioredoxin, thiol-disulfide balance, redox equilibria, redox regulation
MeSH terms: Animals, Cysteine, Cystine, Glutathione, Humans, Models, Biological, Oxidation-Reduction, Signal Transduction, Oxidative Stress, Glutathione Disulfide

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