Mechanism of erythrocyte death in human population exposed to arsenic through drinking water
Mechanism of erythrocyte death in human population exposed to arsenic through drinking water
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DOI：
10.1016/j.taap.2008.02.003
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发表时间：
2008-07-01
影响因子：
3.8
通讯作者：
Biswas, Tuli
中科院分区：
文献类型：
--
作者：
Biswas, Debabrata;Banerjee, Mayukh;Biswas, Tuli
饮用水中的砷污染是世界上最大的自然灾害之一，已成为对人类健康的迫切威胁。在砷暴露人群中，红细胞寿命缩短导致贫血是常见的后遗症。本研究旨在探讨慢性砷暴露致人红细胞死亡的机制。结果显示，在接触者中，光滑的盘状红细胞转变为外翻的棘细胞形式。进一步的变形使可逆棘球细胞转变为不可逆球棘细胞。随着胆固醇/磷脂比例的升高，砷中毒使红细胞膜的微粘度增加，从而阻碍了红细胞膜的弹性，降低了红细胞膜的变形能力。由于砷暴露，花青素540与红细胞膜的结合显著增加，表明细胞膜外层小叶的脂质堆积被破坏，这是由于跨双层磷脂不对称造成的。砷诱导的苏醒以细胞收缩和磷脂酰丝氨酸暴露在细胞表面为特征。此外，代谢饥饿伴随着细胞三磷酸腺苷的耗尽引发了红细胞从循环中的凋亡性移除。还原型谷胱甘肽含量显著降低，表明抗氧化能力有缺陷，丙二醛和蛋白质羰基水平增加，这表明红细胞膜受到氧化损伤。砷中毒干扰了红细胞膜的完整性，最终导致红细胞膜失稳和血红蛋白释放。这项研究描述了在慢性砷暴露期间，红细胞吞噬和溶血都参与了对人类红细胞的破坏。(C)2008 Elsevier Inc.保留所有权利。
Arsenic contamination in drinking water is one of the biggest natural calamities, which has become an imperative threat to human health throughout the world. Abbreviation of erythrocyte lifespan leading to the development of anemia is a common sequel in arsenic exposed population. This study was undertaken to explore the mechanism of cell death in human erythrocytes during chronic arsenic exposure. Results revealed transformation of smooth discoid red cells into evaginated echinocytic form in the exposed individuals. Further distortion converted reversible echinocytes to irreversible spheroechinocytes. Arsenic toxicity increased membrane microviscosity along with an elevation of cholesterol/phospholipid ratio, which hampered the flexibility of red cell membrane and made them less deformable. Significant increase in the binding of merocyanine 540 with erythrocyte membrane due to arsenic exposure indicated disruption of lipid packing in the outer leaflet of the cell membrane resulting from altered transbilayer phospholipid asymmetry. Arsenic induced eryptosis was characterized by cell shrinkage and exposure of phosphatidylserine at the cell surface. Furthermore, metabolic starvation with depletion of cellular ATP triggered apoptotic removal of erythrocytes from circulation. Significant decrease in reduced glutathione content indicating defective antioxidant capacity was coupled with enhancement of malondialdehyde and protein carbonyl levels, which pointed to oxidative damage to erythrocyte membrane. Arsenic toxicity intervened into red cell membrane integrity eventually leading to membrane destabilization and hemoglobin release. The study depicted the involvement of both erythrophagocytosis and hemolysis in the destruction of human erythrocytes during chronic arsenic exposure. (C) 2008 Elsevier Inc. All rights reserved.