The covalent modification of spectrin in red cell membranes by the lipid peroxidation product 4-hydroxy-2-nonenal
The covalent modification of spectrin in red cell membranes by the lipid peroxidation product 4-hydroxy-2-nonenal
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DOI：
10.1016/j.bbrc.2009.12.121
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发表时间：
2010-01-15
影响因子：
3.1
通讯作者：
Inaba, Mutsumi
中科院分区：
文献类型：
--
作者：
Arashiki, Nobuto;Otsuka, Yayoi;Inaba, Mutsumi
Spectrin通过其与膜脂的直接关联以及蛋白质与蛋白质的相互作用增强红细胞膜。谱蛋白的丢失降低了细胞膜的稳定性，导致各种类型的遗传性球形红细胞增多症。然而，对获得性幽灵伤害的了解较少。在这里，我们通过免疫印迹和质谱分析发现，人红细胞中的α -和β -光谱蛋白是脂质过氧化产物4-羟基-2-壬烯醛（HNE）的主要靶点。在不含MgATP的情况下，对制备的红细胞膜幽灵进行HNE处理后，spectrin（特别是α -spectrin）和其他几种膜蛋白中的HNE加合物水平升高。相比之下。MgATP存在下的鬼影制备减少了HNE加合物的形成，优先进行β -谱素修饰，增加了HNE修饰的谱素的交联。将完整的红细胞暴露于HNE导致选择性的HNE-谱蛋白加合物形成，并具有类似的HNE- β -谱蛋白修饰优势。这些发现表明，HNE内聚优先发生在红细胞中骨骼蛋白和脂质双分子层界面处的spectrin中，并提示在生理和疾病条件下，HNE-spectrin加合物聚集导致受损的spectrin和膜脂的挤压。(c) 2009爱思唯尔公司版权所有。
Spectrin strengthens the red cell membrane through its direct association with membrane lipids and through protein-protein interactions. Spectrin loss reduces the membrane stability and results in various types of hereditary spherocytosis. However, less is known about acquired spectrin damage. Here, we showed that alpha- and beta-spectrin in human red cells are the primary targets of the lipid peroxidation product 4-hydroxy-2-nonenal (HNE) by immunoblotting and mass spectrometry analyses. The level of HNE adducts in spectrin (particularly alpha-spectrin) and several other membrane proteins was increased following the HNE treatment of red cell membrane ghosts prepared in the absence of MgATP. In contrast. ghost preparation in the presence of MgATP reduced HNE adduct formation, with preferential beta-spectrin modification and increased cross-linking of the HNE-modified spectrins. Exposure of intact red cells to HNE resulted in selective HNE-spectrin adduct formation with a similar preponderance of HNE-beta-spectrin modifications. These findings indicate that HNE adduction occurs preferentially in spectrin at the interface between the skeletal proteins and lipid bilayer in red cells and suggest that HNE-spectrin adduct aggregation results in the extrusion of damaged spectrin and membrane lipids under physiological and disease conditions. (c) 2009 Elsevier Inc. All rights reserved.