Department of Internal Medicine III, Eberhard-Karls-University Tübingen, Germany.
Department of Vegetative & Clinical Physiology, Institute of Physiology, Eberhard-Karls-University Tübingen, Germany.
FEBS J. 2019 Mar;286(5):826-854. doi: 10.1111/febs.14606. Epub 2018 Aug 18.
The average lifespan of circulating erythrocytes usually exceeds hundred days. Prior to that, however, erythrocytes may be exposed to oxidative stress in the circulation which could cause injury and trigger their suicidal death or eryptosis. Oxidative stress activates Ca -permeable nonselective cation channels in the cell membrane, thus, stimulating Ca entry and subsequent cell membrane scrambling resulting in phosphatidylserine exposure and activation of Ca -sensitive K channels leading to K exit, hyperpolarization, Cl exit, and ultimately cell shrinkage due to loss of KCl and osmotically driven water. While the mechanistic link between oxidative stress and anemia remains ill-defined, several diseases such as diabetes, hepatic failure, malignancy, chronic kidney disease and inflammation have been identified to display both increased oxidative stress as well as eryptosis. Recent compelling evidence suggests that oxidative stress is an important perpetrator in accelerating erythrocyte loss in different systemic conditions and an underlying mechanism for anemia associated with these pathological states. In the present review, we discuss the role of oxidative stress in reducing erythrocyte survival and provide novel insights into the possible use of antioxidants as putative antieryptotic and antianemic agents in a variety of systemic diseases.
循环红细胞的平均寿命通常超过 100 天。然而在此之前，红细胞可能会在循环中暴露于氧化应激下，这可能导致损伤并引发其自杀性死亡或红细胞发生凋亡。氧化应激会激活细胞膜上的 Ca2+通透性非选择性阳离子通道，从而刺激 Ca2+内流，随后导致细胞膜无序化，引发磷脂酰丝氨酸暴露，并激活 Ca2+敏感的 K+通道，导致 K+外流、超极化、Cl-外流，最终由于 KCl 的丢失和渗透驱动的水进入导致细胞收缩。虽然氧化应激与贫血之间的机制联系仍不明确，但已确定一些疾病，如糖尿病、肝衰竭、恶性肿瘤、慢性肾脏病和炎症，既有氧化应激的增加，也有红细胞发生凋亡。最近令人信服的证据表明，氧化应激是加速不同系统性疾病中红细胞丢失的重要因素，也是与这些病理状态相关的贫血的潜在机制。在本综述中，我们讨论了氧化应激在降低红细胞存活率方面的作用，并为抗氧化剂作为各种系统性疾病中潜在的抗红细胞凋亡和抗贫血药物的可能用途提供了新的见解。
