Redox-based regulation of signal transduction: principles, pitfalls, and promises
Open accessAbstract
Oxidants are produced as a by-product of aerobic metabolism, and organisms ranging from prokaryotes to mammals have evolved with an elaborate and redundant complement of antioxidant defenses to confer protection against oxidative insults. Compelling data now exist demonstrating that oxidants are used in physiological settings as signaling molecules with important regulatory functions controlling cell division, migration, contraction, and mediator production. These physiological functions are carried out in an exquisitely regulated and compartmentalized manner by mild oxidants, through subtle oxidative events that involve targeted amino acids in proteins. The precise understanding of the physiological relevance of redox signal transduction has been hampered by the lack of specificity of reagents and the need for chemical derivatization to visualize reversible oxidations. In addition, it is difficult to measure these subtle oxidation events in vivo. This article reviews some of the recent findings that illuminate the significance of redox signaling and exciting future perspectives. We also attempt to highlight some of the current pitfalls and the approaches needed to advance this important area of biochemical and biomedical research.
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Oxidation of two intra- or intermolecular cysteines forms disulfide bridges allowing for conformational changes or oligomerization of proteins.
“Additionally, oxidation of two intra- or intermolecular cysteines forms disulfide bridges allowing for conformational changes or oligomerization of proteins 6, 7.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [6]
The low pKa of the catalytic cysteine allows it to act as a nucleophile for catalysis of dephosphorylation but also makes it a target for oxidation by ROS.
“The low pKa of this cysteine allows it to act as a nucleophile for catalysis of the dephosphorylation reaction, but also makes it a target for oxidation by ROS 6, 7.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [6]
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Winterbourn, C. C. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.08.017 · Cited by 178 · see citing works
- Authors
- Janssen-Heininger, Y. M. W., Mossman, B. T., Heintz, N. H., Forman, H. J., Kalyanaraman, B., Finkel, T., Stamler, J. S., Rhee, S. G., & van der Vliet, A.
- Affiliations
- University of Vermont (US)
- University of California, Merced (US)
- Medical College of Wisconsin (US)
- National Institutes of Health (US)
- Duke University (US)
- Ewha Womans University (KR)
- Corresponding author
- Janssen-Heininger, Yvonne M.W.
- ORCID
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 45
- Issue
- 1
- Pages
- 1-17
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC2453533
- OpenAlex
- W1980385765
- Cited by
- 784
- References
- 246
- Citations by year
- 2026: 12 · 2025: 25 · 2024: 18 · 2023: 26 · 2022: 32 · 2021: 45 · 2020: 47 · 2019: 43 · 2018: 37 · 2017: 39 · 2016: 47 · 2015: 48 · 2014: 50 · 2013: 69 · 2012: 60
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01HL067004, R01 HL60014, P01 HL67004, R01HL074295, R01HL079331, R01HL085646, R01HL068865, R01HL060014)
- National Institute of Environmental Health Sciences (R01ES05511, R01ES005511)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- redox signaling, protein oxidation, antioxidant defense, oxidative stress, cell division, cell migration, cell contraction
- MeSH terms
- Amino Acids, Animals, Gene Expression Regulation, Humans, Hydrogen Peroxide, Oxidation-Reduction, Signal Transduction, Oxidants
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