Membrane peroxidation and methemoglobin formation are both necessary for band 3 clustering: mechanistic insights into human erythrocyte senescence.
Membrane peroxidation and methemoglobin formation are both necessary for band 3 clustering: mechanistic insights into human erythrocyte senescence.
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DOI：
10.1021/bi400405p
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发表时间：
2013-08-27
期刊：
影响因子：
2.9
通讯作者：
Takakuwa, Yuichi
中科院分区：
文献类型：
--
作者：
Arashiki, Nobuto;Kimata, Naoki;Manno, Sumie;Mohandas, Narla;Takakuwa, Yuichi
氧化损伤和带3在膜中的聚集与衰老的人红细胞在其120天寿命结束时从循环中去除有关。然而，导致带3簇形成的生物化学和机械事件尚未完全确定。在这里，我们表明，虽然膜过氧化或MetHb的形成本身都不能诱导带3聚集在人红细胞，他们可以这样做时，在组合作用。我们进一步表明，高铁血红蛋白结合带3的胞质结构域中过氧化，但不是在未经处理的红细胞膜，诱导集群的形成。通过密度梯度程序获得的来自正常人血液的红细胞的分级分离群体使我们能够检查高度富集衰老细胞的亚群。我们已经发现，带3聚类仅是这一小部分的特征，占总循环红细胞的约0.1%。这些衰老细胞的特征在于由于NADH依赖性还原酶活性降低而导致MetHb比例增加，以及累积的氧化膜损伤。这些研究结果使我们能够建立膜过氧化和MetHb形成的综合作用是必要的带3聚类，这是一个非常晚的事件，在红细胞的生活。膜过氧化和高铁血红蛋白的综合作用提出了一个合理的机制，涉及高亲和力的合作结合高铁血红蛋白的氧化带3的细胞质结构域，可能是由于其羰基化，而不是其他形式的氧化损伤。这种修饰导致锚蛋白从带3解离，使得四聚体MetHb能够交联所得的可自由扩散的带3二聚体，形成簇。
Oxidative damage and clustering of band 3 in the membrane have been implicated in the removal of senescent human erythrocytes from the circulation at the end of their 120-day life span. However, the biochemical and mechanistic events leading to band 3 cluster formation have yet to be fully defined. Here we show that while neither membrane peroxidation nor MetHb formation on their own can induce band 3 clustering in the human erythrocytes, they can do so when acting in combination. We further show that MetHb binding to the cytoplasmic domain of band 3 in peroxidized, but not in untreated erythrocyte membranes, induces cluster formation. Age-fractionated populations of erythrocytes from normal human blood, obtained by a density-gradient procedure, have enabled us to examine a subpopulation, highly enriched in senescent cells. We have found that band 3 clustering is a feature of only this small fraction, amounting to ~ 0.1% of total circulating erythrocytes. These senescent cells are characterized by an increased proportion of MetHb as a result of reduced NADH-dependent reductase activity, and accumulated oxidative membrane damage. These findings have enabled us to establish that the combined effects of membrane peroxidation and MetHb formation are necessary for band 3 clustering, and this is a very late event in erythrocyte life. A plausible mechanism for the combined effects of membrane peroxidation and MetHb is proposed, involving high-affinity cooperative binding of MetHb to the cytoplasmic domain of oxidized band 3, probably due to its carbonylation, rather than other forms of oxidative damage. This modification leads to dissociation of ankyrin from the band 3, enabling the tetrameric MetHb to cross-link the resulting freely diffusible band 3 dimers, with formation of clusters.
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影响因子：
56.9
作者：
LOW, PS;WAUGH, SM;DRENCKHAHN, D
通讯作者：
DRENCKHAHN, D
DOI：
10.1016/j.bbrc.2009.12.121
发表时间：
2010-01-15
影响因子：
3.1
作者：
Arashiki, Nobuto;Otsuka, Yayoi;Inaba, Mutsumi
通讯作者：
Inaba, Mutsumi
影响因子：
20.3
作者：
MANNU, F;ARESE, P;TURRINI, F
通讯作者：
TURRINI, F
影响因子：
4.1
作者：
Pantaleo, Antonella;Ferru, Emanuela;Turrini, Franco
通讯作者：
Turrini, Franco
影响因子：
13.6
作者：
Pantaleo, Antonella;Giribaldi, Giuliana;Turrini, Franco
通讯作者：
Turrini, Franco