The DOI matches its Crossref record; 212 of the 212 references it cites were found in a registry or an index.
Thiol chemistry and specificity in redox signaling
Abstract
Exposure of cells to sublethal oxidative stress results in the modulation of various signaling pathways. Oxidants can activate and inactivate transcription factors, membrane channels, and metabolic enzymes, and regulate calcium-dependent and phosphorylation signaling pathways. Oxidation and reduction of thiol proteins are thought to be the major mechanisms by which reactive oxidants integrate into cellular signal transduction pathways. This review focuses on mechanisms for sensing and transmitting redox signals, from the perspective of their chemical reactivity with specific oxidants. We discuss substrate preferences for different oxidants and how the kinetics of these reactions determines how each oxidant will react in a cell. This kinetic approach helps to identify initial oxidant-sensitive targets and elucidate mechanisms involved in transmission of redox signals. It indicates that only those proteins with very high reactivity, such as peroxiredoxins, are likely to be direct targets for hydrogen peroxide. Other more modestly reactive thiol proteins such as protein tyrosine phosphatases are more likely to become oxidized by an indirect mechanism. The review also examines oxidative changes observed during receptor-mediated signaling, the strengths and limitations of detection methods for reactive oxidant production, and the evidence for hydrogen peroxide acting as the second messenger. We discuss areas where observations in cell systems can be rationalized with the reactivity of specific oxidants and where further work is needed to understand the mechanisms involved.
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“The highly effective mitochondrial antioxidative defense system encompasses the thioredoxin/peroxiredoxin system as well as the glutathione/glutathione peroxidase system (overview in [22,117]).”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [117]
In the citing paper
“Excessive H2O2 production, however, leads to further oxidation of the sulfenic group (Cys-SOH) to sulfinic (Cys-SO2H) and sulfonic groups (Cys-SO3H), a process that is irreversible and results in protein malfunction [55].”
From Functions of ROS in Macrophages and Antimicrobial Immunity (2021) · cites this paper as [55]
In the citing paper
“At low concentrations, ROS are essential participants in cell signaling (136, 323, 450), whereas excess ROS can disrupt normal cellular function and promote damage to cellular lipids, nucleic acids, and proteins.”
From Redox regulation of mitochondrial function (2012) · cites this paper as [450]
In the citing paper
“lack of mitochondrial oxidant production leads to diminished cell signaling in response to growth factors, such as insulin, and decreases the formation of necessary protein disulfides (169, 264, 284, 450, 464).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [450]
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Metadata
- Authors
- Winterbourn, C. C., & Hampton, M. B.
- Affiliations
- University of Otago (NZ)
- Corresponding author
- Winterbourn, Christine C.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2008-09
- Volume
- 45
- Issue
- 5
- Pages
- 549-561
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2068102085
- Cited by
- 1,226
- References
- 212
- Citations by year
- 2026: 30 · 2025: 38 · 2024: 54 · 2023: 55 · 2022: 67 · 2021: 66 · 2020: 75 · 2019: 74 · 2018: 75 · 2017: 82 · 2016: 66 · 2015: 80 · 2014: 87 · 2013: 101 · 2012: 84
- FWCI
- 4.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- 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 › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- thiol chemistry, redox signaling, oxidative stress, hydrogen peroxide, peroxiredoxin, protein tyrosine phosphatase, second messengers, receptor signaling
- MeSH terms
- Animals, Humans, Models, Biological, Oxidation-Reduction, Substrate Specificity, Sulfhydryl Compounds, Signal Transduction, Oxidants, Reactive Oxygen Species
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