Verapamil prevents impairment in filterability of human erythrocytes exposed to oxidative stress.
Verapamil prevents impairment in filterability of human erythrocytes exposed to oxidative stress.
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维拉帕米可防止暴露于氧化应激的人红细胞过滤性受损。
DOI：
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
N. Uyesaka
中科院分区：
文献类型：
--
作者：
Kazuhiko Okamoto;T. Maruyama;Y. Kaji;M. Harada;S. Mawatari;T. Fujino;N. Uyesaka
使用叔丁基过氧化氢 (tBHP) 研究氧化应激对完整人红细胞的影响。红细胞暴露于 tBHP 会导致过滤性以时间依赖性方式显着降低。暴露于 tBHP 的红细胞还表现出平均红细胞体积的增加和高铁血红蛋白 (met-Hb) 的显着形成，而没有出现任何形成亨氏小体的半色素。高效液相色谱表明，tBHP 处理的红细胞膜磷脂、磷脂酰乙醇胺 (PE) 明显减少。抗坏血酸预处理可以抑制 PE 的降低，但维拉帕米则不能。 tBHP 处理的红细胞膜的 SDS 聚丙烯酰胺凝胶电泳显示血影蛋白、条带 3、条带 4.2 和条带 4.5 降解，并伴有低分子量产物的出现。用维拉帕米或抗坏血酸预处理并不能阻止膜蛋白的降解。然而，在细胞外 Ca2+ 存在的情况下，用维拉帕米而非抗坏血酸预处理显示出对 tBHP 诱导的滤过性损害的显着抑制。因此，本研究表明，维拉帕米是再灌注治疗中的一种有效药物，基于过滤性降低、met-Hb 形成和膜完整性受损之间的密切联系，在防止氧化损伤方面发挥着重要作用。
Effects of oxidative stress on intact human erythrocytes were investigated using tert-butyl hydroperoxide (tBHP). Exposure of erythrocytes to tBHP caused a marked decrease in filterability in a time-dependent manner. Erythrocytes exposed to tBHP also show an increase in mean corpuscular volume and a remarkable formation of methemoglobin (met-Hb) without any appearance of hemichromes that form Heinz bodies. High performance liquid chromatography demonstrated that the tBHP-treated erythrocytes exhibited an apparent decrease in the membrane phospholipid, phosphatidylethanolamine (PE). The decrease in PE was inhibited by pretreatment with ascorbate, but not with verapamil. SDS-polyacrylamide gel electrophoresis of the tBHP-treated erythrocyte membrane showed a degradation of spectrin, band 3, band 4.2, and band 4.5, accompanied by the appearance of low-molecular-weight products. The degradation of the membrane proteins was not prevented by pretreatment with verapamil or ascorbate. However, the pretreatment with verapamil but not with ascorbate revealed significant inhibition of the tBHP-induced impairment in filterability in the presence of extracellular Ca2+. Thus, the present study shows that verapamil, a potent drug in reperfusion therapy, plays an important role in protection against oxidative injury, based on a close linkage among decreased filterability, met-Hb formation, and impaired membrane integrity.
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影响因子：
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DOI：
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DOI：
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