Morabito Rossana, Romano Orazio, La Spada Giuseppa, Marino Angela
Department of Human and Social Sciences, University of Messina, Messina, Italy.
BromaTech S.r.l., Giarre, Italy.
PLoS One. 2016 Jan 8;11(1):e0146485. doi: 10.1371/journal.pone.0146485. eCollection 2016.
The aim of the present investigation was to verify the effect of H2O2-induced oxidative stress on SO4= uptake through Band 3 protein, responsible for Cl-/HCO3- as well as for cell membrane deformability, due to its cross link with cytoskeletal proteins. The role of cytoplasmic proteins binding to Band 3 protein has been also considered by assaying H2O2 effects on hemoglobin-free resealed ghosts of erythrocytes. Oxidative conditions were induced by 30 min exposure of human erythrocytes to different H2O2 concentrations (10 to 300 μM), with or without GSH (glutathione, 2 mM) or curcumin (10 μM), compounds with proved antioxidant properties. Since SO4= influx through Band 3 protein is slower and better controllable than Cl- or HCO3- exchange, the rate constant for SO4= uptake was measured to prove anion transport efficiency, while MDA (malondialdehyde) levels and -SH groups were estimated to quantify the effect of oxidative stress. H2O2 induced a significant decrease in rate constant for SO4= uptake at both 100 and 300 μM H2O2. This reduction, observed in erythrocytes but not in resealed ghosts and associated to increase in neither MDA levels nor in -SH groups, was impaired by both curcumin and GSH, whereas only curcumin effectively restored H2O2-induced changes in erythrocytes shape. Our results show that: i) 30 min exposure to 300 μM H2O2 reduced SO4= uptake in human erythrocytes; ii) oxidative damage was revealed by the reduction in rate constant for SO4= uptake, but not by MDA or -SH groups levels; iii) the damage was produced via cytoplasmic components which cross link with Band 3 protein; iv) the natural antioxidant curcumin may be useful in protecting erythrocytes from oxidative injury; v) SO4= uptake through Band 3 protein may be reasonably suggested as a tool to monitor erythrocytes function under oxidative conditions possibly deriving from alcohol consumption, use of drugs, radiographic contrast media administration, hyperglicemia or neurodegenerative diseases.
本研究的目的是验证过氧化氢(H2O2)诱导的氧化应激对通过带3蛋白摄取硫酸根离子(SO4=)的影响。带3蛋白负责氯离子(Cl-)/碳酸氢根离子(HCO3-)交换以及细胞膜的可变形性,这是由于它与细胞骨架蛋白交联。通过检测H2O2对无血红蛋白的红细胞重封膜泡的影响,也探讨了细胞质蛋白与带3蛋白结合的作用。通过将人红细胞暴露于不同浓度的H2O2(10至300μM)30分钟来诱导氧化条件,同时添加或不添加谷胱甘肽(GSH,2 mM)或姜黄素(10μM),这两种化合物都具有抗氧化特性。由于通过带3蛋白的硫酸根离子内流比氯离子或碳酸氢根离子交换更慢且更易于控制,因此测量硫酸根离子摄取的速率常数以证明阴离子转运效率,同时估计丙二醛(MDA)水平和巯基(-SH)含量以量化氧化应激的影响。在100μM和300μM的H2O2浓度下,H2O2均导致硫酸根离子摄取的速率常数显著降低。这种降低在红细胞中观察到,但在重封膜泡中未观察到,并且与MDA水平和巯基含量的增加均无关,姜黄素和GSH均可减轻这种降低,而只有姜黄素能有效恢复H2O2诱导的红细胞形状变化。我们的结果表明:i)暴露于300μM H2O2 30分钟会降低人红细胞中硫酸根离子的摄取;ii)硫酸根离子摄取速率常数的降低揭示了氧化损伤,但MDA或巯基含量水平并未显示氧化损伤;iii)损伤是通过与带3蛋白交联的细胞质成分产生的;iv)天然抗氧化剂姜黄素可能有助于保护红细胞免受氧化损伤;v)通过带3蛋白摄取硫酸根离子可能是一种合理的工具,用于监测在可能由饮酒、药物使用、放射造影剂给药、高血糖或神经退行性疾病引起的氧化条件下的红细胞功能。