Cysteine–iron promotes arginase activity by driving the Fenton reaction
Open accessAbstract
Impairment of nitric oxide bioavailability secondary to increased arginase activity and overproduction of reactive oxygen species (ROS) is thought to be a major cause of vascular complications in sickle cell disease (SCD). However, the role of ROS in the induction of arginase activity is unknown. This study investigated whether the mechanism of arginase activation involves the ROS produced during oxidative stress. Our study reveals that cysteine-iron dose-dependently stimulated arginase activity with a corresponding increase in (.)OH radical formation. The ()OH radicals produced were significantly inhibited by salicylic acid derivatives and superoxide dismutase. Surprisingly, the inhibition of (.)OH radicals parallels the inhibition of arginase activity, thus suggesting the role of cysteine-iron in the stimulation of arginase via the Fenton reaction. This is the first evidence demonstrating the participation of (.)OH radicals in the stimulation of arginase activity, and thus provides novel avenues for therapeutic modalities in hemoglobinopathies and other inflammation-mediated diseases.
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In physiology, perhaps the most common source of Fenton chemistry is the presence of increased concentrations of free iron and/or copper.
“In physiology, perhaps the most common source of Fenton chemistry is the presence of increased concentrations of free iron and/or copper (122, 458, 959).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [458]
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- Authors
- Iyamu, E. W., Perdew, H., & Woods, G. M.
- Affiliations
- Children's Mercy Hospital (US)
- Corresponding author
- Iyamu, Efemwonkiekie W.
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 376
- Issue
- 1
- Pages
- 116-120
- ISSN
- 0006-291X (ISSN-L)
- PMC
- PMC2585818
- OpenAlex
- W2095470369
- Cited by
- 26
- References
- 26
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 1 · 2014: 1 · 2013: 1 · 2012: 3
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1k01hl076695-01)
- National Heart, Lung, and Blood Institute (K01 HL076695, K01 HL076695-01)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- arginase, Fenton reaction, hydroxyl radicals, reactive oxygen species, oxidative stress, nitric oxide bioavailability, sickle cell disease, salicylates, superoxide dismutase, hemoglobinopathies, enzyme activation
- MeSH terms
- Anemia, Sickle Cell, Arginase, Cysteine, Enzyme Activation, Erythrocytes, Humans, Iron, Superoxides, Superoxide Dismutase, Salicylic Acid
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