Inborn defects in the antioxidant systems of human red blood cells
Abstract
Red blood cells (RBCs) contain large amounts of iron and operate in highly oxygenated tissues. As a result, these cells encounter a continuous oxidative stress. Protective mechanisms against oxidation include prevention of formation of reactive oxygen species (ROS), scavenging of various forms of ROS, and repair of oxidized cellular contents. In general, a partial defect in any of these systems can harm RBCs and promote senescence, but is without chronic hemolytic complaints. In this review we summarize the often rare inborn defects that interfere with the various protective mechanisms present in RBCs. NADPH is the main source of reduction equivalents in RBCs, used by most of the protective systems. When NADPH becomes limiting, red cells are prone to being damaged. In many of the severe RBC enzyme deficiencies, a lack of protective enzyme activity is frustrating erythropoiesis or is not restricted to RBCs. Common hereditary RBC disorders, such as thalassemia, sickle-cell trait, and unstable hemoglobins, give rise to increased oxidative stress caused by free heme and iron generated from hemoglobin. The beneficial effect of thalassemia minor, sickle-cell trait, and glucose-6-phosphate dehydrogenase deficiency on survival of malaria infection may well be due to the shared feature of enhanced oxidative stress. This may inhibit parasite growth, enhance uptake of infected RBCs by spleen macrophages, and/or cause less cytoadherence of the infected cells to capillary endothelium.
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GSH can be utilized for the reduction of ascorbate, oxidized proteins, and oxidized lipids.
“In healthy human RBCs, 90%–95% of glutathione is present in the reduced form GSH (200) that can be utilized for the reduction of ascorbate, oxidized proteins, and oxidized lipids (184).”
From Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia (2017) · cites this paper as [184]
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- Authors
- van Zwieten, R., Verhoeven, A. J., & Roos, D.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Sanquin (NL)
- ORCID
- Roos, Dirk
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 67
- Pages
- 377-386
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2142563528
- Cited by
- 179
- References
- 166
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 11 · 2023: 16 · 2022: 43 · 2021: 10 · 2020: 10 · 2019: 17 · 2018: 8 · 2017: 13 · 2016: 11 · 2015: 11 · 2014: 10
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal Health and Biochemistry
- Keywords
- oxidative stress, NADPH, reactive oxygen species scavenging, erythropoiesis, thalassemia, sickle cell trait, unstable hemoglobin, glucose-6-phosphate dehydrogenase deficiency, malaria resistance, heme, iron, erythrocyte senescence
- MeSH terms
- Anemia, Hemolytic, Antioxidants, Erythrocytes, Erythropoiesis, Glucosephosphate Dehydrogenase Deficiency, Glutathione, Humans, Malaria, NADP, Oxidation-Reduction, Sickle Cell Trait, Thalassemia, Reactive Oxygen Species, Oxidative Stress
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