Cited by 179Redox biology and oxidative stressHemoglobinopathies and Related DisordersNeonatal Health and Biochemistry

Inborn defects in the antioxidant systems of human red blood cells

van Zwieten, Rob, Verhoeven, Arthur J., Roos, Dirk·2014·Free Radical Biology and Medicine

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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Crossref · 10.1016/j.freeradbiomed.2013.11.022

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Authors
van Zwieten, R., Verhoeven, A. J., & Roos, D.
Affiliations
  • Amsterdam UMC Location University of Amsterdam (NL)
  • Sanquin (NL)
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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