The impact of erythrocyte age on eryptosis

The impact of erythrocyte age on eryptosis
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DOI:
10.1111/j.1365-2141.2012.09100.x
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发表时间:
2012-06-01
影响因子:
6.5
通讯作者:
Bosman, Giel J. C. G. M.
Bosman, Giel J. C. G. M.
中科院分区:
医学2区
文献类型:
--
作者:
Ghashghaeinia, Mehrdad;Cluitmans, Judith C. A.;Bosman, Giel J. C. G. M.

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成熟的循环红细胞会经历衰老​​,这将其寿命限制在大约 120 天。受伤后,红细胞可能会发生自杀性红细胞死亡或红细胞凋亡,这可能会加速衰老并缩短其生存时间。红斑狼疮定义为细胞收缩和细胞表面磷脂酰丝氨酸的暴露。红细胞凋亡的触发因素包括氧化应激。本研究探讨红细胞年龄对红细胞病相对易感性的影响。根据与年龄相关的密度和体积差异,红细胞被分为五个部分。细胞膜扰乱是通过红细胞表面膜联蛋白 V 与磷脂酰丝氨酸的结合、前向散射的细胞体积以及 Fluo-3 依赖性荧光的 Ca2+ 水平来估计的。此外,还通过酶/比色法测量谷胱甘肽 (GSH) 浓度。在林格溶液中孵育 48 小时后,Annexin V 结合随着红细胞年龄的增加而显着增加。这些差异并不伴随着谷胱甘肽浓度的改变,而是通过在体外添加抗氧化剂 N-乙酰基-L-半胱氨酸来逆转。此外,N-乙酰基-L-半胱氨酸显着延长了小鼠体内循环红细胞的半衰期。因此,对红细胞的易感性随着红细胞年龄的增长而增加,并且这种效应至少部分归因于对氧化应激的敏感性增强。
Mature, circulating erythrocytes undergo senescence, which limits their life span to approximately 120 d. Upon injury, erythrocytes may undergo suicidal erythrocyte death or eryptosis, which may accelerate senescence and shorten their survival. Eryptosis is defined as cell shrinkage and exposure of phosphatidylserine at the cell surface. Triggers of eryptosis include oxidative stress. The present study addresses the impact of erythrocyte age on the relative susceptibility to eryptosis. Erythrocytes were separated into five fractions, based on age-associated differences in density and volume. Cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, the cell volume from forward scatter, and the Ca2+ level from Fluo-3-dependent fluorescence. In addition, glutathione (GSH) concentrations were measured by an enzymatic/colourimetric method. After 48 h incubation in Ringer solution, Annexin V binding increased significantly with erythrocyte age. The differences were not accompanied by altered GSH concentrations, but were reversed by addition of the antioxidant N-acetyl-l-cysteine in vitro. Also, N-acetyl-l-cysteine significantly prolonged the half-life of circulating mouse erythrocytes in vivo. Thus, the susceptibility to eryptosis increases with the age of the erythrocytes, and this effect is at least partially due to enhanced sensitivity to oxidative stress.