1. Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production
- Author
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Yoshihito Iuchi, Masanobu Kobayashi, Kunishige Onuma, Tadashi Onoda, Junichi Fujii, Hironobu Asao, and Futoshi Okada
- Subjects
medicine.medical_specialty ,Erythrocytes ,Antioxidant ,medicine.medical_treatment ,SOD1 ,Oxidative phosphorylation ,Biology ,medicine.disease_cause ,Biochemistry ,Antioxidants ,Superoxide dismutase ,Mice ,Superoxide Dismutase-1 ,Internal medicine ,medicine ,Animals ,Molecular Biology ,Autoantibodies ,Inflammation ,Mice, Knockout ,chemistry.chemical_classification ,Reactive oxygen species ,Superoxide Dismutase ,Autoantibody ,Anemia ,Cell Biology ,Acetylcysteine ,Oxidative Stress ,Phenotype ,Endocrinology ,chemistry ,Immunology ,biology.protein ,Erythropoiesis ,Oxidation-Reduction ,Oxidative stress ,Research Article - Abstract
Reactive oxygen species are involved in the aging process and diseases. Despite the important role of Cu/Zn SOD (superoxide dismutase) encoded by SOD1, 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 SOD1 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 II, 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. more...
- Published
- 2007
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