The Role of RBC Oxidative Stress in Sickle Cell Disease: From the Molecular Basis to Pathologic Implications.
The Role of RBC Oxidative Stress in Sickle Cell Disease: From the Molecular Basis to Pathologic Implications.
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DOI：
10.3390/antiox10101608
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发表时间：
2021-10-13
期刊：
影响因子：
--
通讯作者：
Zennadi R
中科院分区：
文献类型：
--
作者：
Wang Q;Zennadi R
镰状细胞病（SCD）是一种遗传性单基因疾病，是世界上最常见的严重血红蛋白病。SCD的特征在于β-珠蛋白基因中的点突变，其导致血红蛋白（Hb）S产生，从而导致镰状红细胞（RBC）内的多种机制和表型变化。在SCD中，镰状红细胞是疾病的根本原因，并且它们是氧化应激的主要来源，因为镰状红细胞氧化还原状态由于促氧化剂和抗氧化剂之间的不平衡而受损。这种氧化还原状态的不平衡是由恒定的内源性Hb自氧化和NADPH氧化酶活化以及抗氧化防御系统的缺乏引起的镰状RBC内活性氧（ROS）的连续产生的结果。镰状RBC内未中和的ROS的积累影响RBC膜结构和功能，导致膜完整性缺陷、低变形性、磷脂酰丝氨酸暴露和微泡释放。这些氧化应激相关的RBC表型修饰因此引起了涉及多系统表现的无数生理变化。因此，SCD中的RBC氧化应激可最终引发涉及器官损伤的主要过程。本文讨论了镰状红细胞活性氧的产生及其在SCD病理生理学中的调节作用。
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.
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