HEME DEGRADATION IN THE PRESENCE OF GLUTATHIONE - A PROPOSED MECHANISM TO ACCOUNT FOR THE HIGH-LEVELS OF NONHEME IRON FOUND IN THE MEMBRANES OF HEMOGLOBINOPATHIC RED-BLOOD-CELLS
HEME DEGRADATION IN THE PRESENCE OF GLUTATHIONE - A PROPOSED MECHANISM TO ACCOUNT FOR THE HIGH-LEVELS OF NONHEME IRON FOUND IN THE MEMBRANES OF HEMOGLOBINOPATHIC RED-BLOOD-CELLS
复制标题
DOI：
10.1074/jbc.270.42.24876
复制
发表时间：
1995-10-20
影响因子：
4.8
通讯作者：
GINSBURG, H
中科院分区：
文献类型：
--
作者：
ATAMNA, H;GINSBURG, H
不稳定的血红蛋白和氧化条件往往会产生血红素，这些血红素明显释放到红细胞膜上，从而导致脂质过氧化和细胞溶解。在这种情况下也发现了高水平的非血红素铁，但这种铁的来源是不确定的。在目前的工作中，我们表明，还原型谷胱甘肽（GSH）是能够降解血红素在溶液中的最佳pH值为7。降解取决于氧的存在和血红素和GSH的浓度。它被抑制过氧化氢酶和超氧化物歧化酶，暗示perferryl反应物种参与血红素降解的过程中。血红素在pH 7和37 ° C下的降解是快速的（t（1/2）= 70 s），并导致铁从血红素中释放。溶解在红细胞血影中的血红素也被GSH降解，伴随着非血红素铁的增加，其中大部分（75%）仍然与细胞膜相关。装载的完整的红细胞与血红素的膜相关的血红素的时间依赖性减少，并导致加速的己糖一磷酸分流由于生产的H2 O2和细胞内GSH的氧化。大多数的己糖磷酸途径的激活是由于铁的氧化还原循环，因为铁螯合剂抑制它相当大。这些结果解释了镰状细胞膜中发现的非血红素铁的起源以及在这些和其他异常红细胞中观察到的氧化应激。
Unstable hemoglobins and oxidative conditions tend to produce hemichromes which demonstrably release their heme to the erythrocyte membrane, with consequent lipid peroxidation and cell lysis. High levels of non-heme iron are also found in such circumstances, but the origin of this iron is uncertain. In the present work, we show that reduced glutathione (GSH) is able to degrade heme in solution with a pH optimum of 7. Degradation depended on the presence of oxygen and on heme and GSH concentrations. It was inhibited by catalase and superoxide dismutase, implicating the involvement of perferryl reactive species in the process of heme degradation. Heme degradation at pH 7 and 37 degrees C is rapid (t(1/2) = 70 s) and results in the release of iron from heme. Heme that was dissolved in red blood cell ghosts is also degraded by GSH with a concomitant increase in non-heme iron, most of which (75%) remains associated with the cell membrane. Loading of intact erythrocytes with heme was followed by time-dependent decrease of membrane-associated heme and caused an acceleration of the hexose monophosphate shunt due to the production of H2O2 and the oxidation of intracellular GSH. Most of the activation of the hexose monophosphate pathway was due to redox cycling of iron, since iron chelators inhibited it considerably. These results explain the origin of non-heme iron found in the membrane of sickle cells and the oxidative stress that is observed in these and other abnormal erythrocytes.