The Role of RBC Oxidative Stress in Sickle Cell Disease: From the Molecular Basis to Pathologic Implications
Sickle cell disease (SCD) is an inherited monogenic disorder and the most common severe hemoglobinopathy in the world. SCD is characterized by a point mutation in the β-globin gene, which results in hemoglobin (Hb) S production, leading to a variety of mechanistic and phenotypic changes within the s...
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MDPI AG
2021-10-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/10/1608 |
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| author | Qinhong Wang Rahima Zennadi |
| author_facet | Qinhong Wang Rahima Zennadi |
| author_sort | Qinhong Wang |
| collection | DOAJ |
| description | Sickle cell disease (SCD) is an inherited monogenic disorder and the most common severe hemoglobinopathy in the world. SCD is characterized by a point mutation in the β-globin gene, which results in hemoglobin (Hb) S production, leading to a variety of mechanistic and phenotypic changes within the sickle red blood cell (RBC). In SCD, the sickle RBCs are the root cause of the disease and they are a primary source of oxidative stress since sickle RBC redox state is compromised due to an imbalance between prooxidants and antioxidants. This imbalance in redox state is a result of a continuous production of reactive oxygen species (ROS) within the sickle RBC caused by the constant endogenous Hb autoxidation and NADPH oxidase activation, as well as by a deficiency in the antioxidant defense system. Accumulation of non-neutralized ROS within the sickle RBCs affects RBC membrane structure and function, leading to membrane integrity deficiency, low deformability, phosphatidylserine exposure, and release of micro-vesicles. These oxidative stress-associated RBC phenotypic modifications consequently evoke a myriad of physiological changes involved in multi-system manifestations. Thus, RBC oxidative stress in SCD can ultimately instigate major processes involved in organ damage. The critical role of the sickle RBC ROS production and its regulation in SCD pathophysiology are discussed here. |
| first_indexed | 2024-03-10T06:45:48Z |
| format | Article |
| id | doaj.art-e2e8511847fe4cb495909a75ffb37d26 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T06:45:48Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-e2e8511847fe4cb495909a75ffb37d262023-11-22T17:16:39ZengMDPI AGAntioxidants2076-39212021-10-011010160810.3390/antiox10101608The Role of RBC Oxidative Stress in Sickle Cell Disease: From the Molecular Basis to Pathologic ImplicationsQinhong Wang0Rahima Zennadi1Duke Comprehensive Sickle Cell Center and Division of Hematology, Department of Medicine, School of Medicine, Duke University, Durham, NC 27710, USADuke Comprehensive Sickle Cell Center and Division of Hematology, Department of Medicine, School of Medicine, Duke University, Durham, NC 27710, USASickle cell disease (SCD) is an inherited monogenic disorder and the most common severe hemoglobinopathy in the world. SCD is characterized by a point mutation in the β-globin gene, which results in hemoglobin (Hb) S production, leading to a variety of mechanistic and phenotypic changes within the sickle red blood cell (RBC). In SCD, the sickle RBCs are the root cause of the disease and they are a primary source of oxidative stress since sickle RBC redox state is compromised due to an imbalance between prooxidants and antioxidants. This imbalance in redox state is a result of a continuous production of reactive oxygen species (ROS) within the sickle RBC caused by the constant endogenous Hb autoxidation and NADPH oxidase activation, as well as by a deficiency in the antioxidant defense system. Accumulation of non-neutralized ROS within the sickle RBCs affects RBC membrane structure and function, leading to membrane integrity deficiency, low deformability, phosphatidylserine exposure, and release of micro-vesicles. These oxidative stress-associated RBC phenotypic modifications consequently evoke a myriad of physiological changes involved in multi-system manifestations. Thus, RBC oxidative stress in SCD can ultimately instigate major processes involved in organ damage. The critical role of the sickle RBC ROS production and its regulation in SCD pathophysiology are discussed here.https://www.mdpi.com/2076-3921/10/10/1608reactive oxygen speciesNADPH oxidasered blood cellssickle cell disease |
| spellingShingle | Qinhong Wang Rahima Zennadi The Role of RBC Oxidative Stress in Sickle Cell Disease: From the Molecular Basis to Pathologic Implications Antioxidants reactive oxygen species NADPH oxidase red blood cells sickle cell disease |
| title | The Role of RBC Oxidative Stress in Sickle Cell Disease: From the Molecular Basis to Pathologic Implications |
| title_full | The Role of RBC Oxidative Stress in Sickle Cell Disease: From the Molecular Basis to Pathologic Implications |
| title_fullStr | The Role of RBC Oxidative Stress in Sickle Cell Disease: From the Molecular Basis to Pathologic Implications |
| title_full_unstemmed | The Role of RBC Oxidative Stress in Sickle Cell Disease: From the Molecular Basis to Pathologic Implications |
| title_short | The Role of RBC Oxidative Stress in Sickle Cell Disease: From the Molecular Basis to Pathologic Implications |
| title_sort | role of rbc oxidative stress in sickle cell disease from the molecular basis to pathologic implications |
| topic | reactive oxygen species NADPH oxidase red blood cells sickle cell disease |
| url | https://www.mdpi.com/2076-3921/10/10/1608 |
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