Angiotensin II-Induced Erythrocyte Senescence Contributes to Oxidative Stress
Angiotensin II-Induced Erythrocyte Senescence Contributes to Oxidative Stress
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DOI：
10.1089/rej.2021.0054
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发表时间：
2022-02-01
影响因子：
2.6
通讯作者：
Shen, Weili
中科院分区：
文献类型：
--
作者：
Huang, Chenglin;Gao, Jing;Shen, Weili
氧化应激可能是红细胞衰老的重要原因。血管紧张素 II (Ang II) 最近被证明可以促进血管细胞衰老。然而，其对红细胞的影响仍不清楚。本研究旨在探讨 Ang II 通过氧化应激调节红细胞寿命的作用。实验在 C57/BL6J 小鼠中进行，注射 Ang II（每分钟 1500 ng/kg）或盐水 7 天。输注Ang II后，我们发现Ang II增加了红细胞数量、血红蛋白和红细胞分布宽度。这些差异伴随着谷胱甘肽 (GSH) 的减少和丙二醛 (MDA) 浓度的增加。在体外，Ang II 处理 24 小时后，红细胞表面 CD47 表达减少，磷脂酰丝氨酸暴露增加。与此同时，Ang II 降低了抗氧化酶的水平，包括 Cu/ZnSOD、过氧化氢酶和过氧化物酶 2 (PRDX2)。通过添加抗氧化剂 N-乙酰基-L-半胱氨酸或 Ang II 1 型 (AT1) 受体阻滞剂氯沙坦，可以逆转这些影响。此外，Ang II 治疗增加了红细胞膜中的促炎氧脂素，包括羟基二十碳四烯酸 (HETE) 和二羟基十八碳烯酸 (DiHOME)。总的来说，Ang II 会诱导红细胞衰老和对红细胞的易感性，部分原因是氧化应激增强。
Oxidative stress may be an important cause of erythrocyte senescence. Angiotensin II (Ang II) has recently been shown to promote vascular cell senescence. However, its effects on erythrocytes remain unclear. This study aims at investigating the role of Ang II in regulating erythrocyte lifespan through oxidative stress. Experiments were performed in C57/BL6J mice infused with Ang II (1500 ng/kg per minute) or saline for 7 days. After Ang II infusion, we found that Ang II increased erythrocyte number, hemoglobin, and red blood cell distribution width. These differences were accompanied by a decrease in glutathione (GSH) and an increase in malondialdehyde (MDA) concentration. In vitro, after 24 hours of Ang II treatment, erythrocytes showed reduced surface expression of CD47 and increased phosphatidylserine exposure. In parallel, Ang II reduced the levels of antioxidant enzymes, including Cu/ZnSOD, catalase, and peroxidase 2 (PRDX2). These effects were reversed by the addition of the antioxidant N-acetyl-L-cysteine or the Ang II type 1 (AT1) receptor blocker losartan. In addition, Ang II treatment increased pro-inflammatory oxylipin, including hydroxyeicosatetraenoic acids (HETEs) and dihydroxyoctadecenoic acids (DiHOMEs), in the erythrocyte membranes. Collectively, Ang II induced erythrocyte senescence and susceptibility to eryptosis, partially due to enhanced oxidative stress.