Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production
Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production
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DOI：
10.1042/bj20061386
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发表时间：
2007-03-01
影响因子：
4.1
通讯作者：
Fujii, Junichi
中科院分区：
文献类型：
--
作者：
Iuchi, Yoshihito;Okada, Futoshi;Fujii, Junichi
活性氧参与衰老过程和疾病。尽管由SOD编码的Cu/Zn SOD（超氧化物歧化酶）具有重要作用，但SOD 1（-/-）小鼠似乎在常规饲养条件下正常生长。在本文中，我们报告了一个新的发现，显示了一个独特的连接之间的氧化应激红细胞和生产的自身抗体对红细胞的SOD 1（-/-）小鼠。有证据表明，SOD 1主要是通过抑制氧化应激来维持红细胞寿命所必需的。SOD]缺乏通过蛋白质和脂质的氧化修饰导致红细胞脆弱性增加，从而导致贫血和红细胞生成的代偿性激活。氧化红细胞的持续破坏似乎诱导针对某些红细胞组分（例如碳酸酐酶11）的自身抗体的形成，并且免疫复合物沉积在肾小球中。抗氧化剂N-乙酰半胱氨酸的施用抑制红细胞氧化，改善贫血，并抑制自身抗体的产生。这些数据表明，红细胞中高水平的氧化应激增加了自身抗体的产生，可能导致自身免疫反应，并且摄入抗氧化剂将通过维持红细胞中适当的氧化还原平衡来防止某些自身免疫反应。
Reactive oxygen species are involved in the aging process and diseases. Despite the important role of Cu/Zn SOD (superoxide dismutase) encoded by SOD], SOD1(-/-) mice appear to grow normally under conventional breeding conditions. In the present paper we report on a novel finding showing a distinct connection between oxidative stress in erythrocytes and the production of autoantibodies against erythrocytes in SOD1(-/-) mice. Evidence is presented to show that SOD1 is primarily required for maintaining erythrocyte lifespan by suppressing oxidative stress. A SOD] deficiency led to an increased erythrocyte vulnerability by the oxidative modification of proteins and lipids, resulting in anaemia and compensatory activation of erythropoiesis. The continuous destruction of oxidized erythrocytes appears to induce the formation of autoantibodies against certain erythrocyte components, e.g. carbonic anhydrase 11, and the immune complex is deposited in the glomeruli. The administration of an antioxidant, N-acetylcysteine, suppressed erythrocyte oxidation, ameliorated the anaemia, and inhibited the production of autoantibodies. These data imply that a high level of oxidative stress in erythrocytes increases the production of autoantibodies, possibly leading to an autoimmune response, and that the intake of antioxidants would prevent certain autoimmune responses by maintaining an appropriate redox balance in erythrocytes.