Iron release, membrane protein oxidation and erythrocyte ageing

Signorini, Cinzia; Ferrali, Marco; Ciccoli, Lucia; Sugherini, L.; Magnani, Agnese; Comporti, Mario

doi:10.1016/0014-5793(95)00235-2

Cited by 69 publications

(36 citation statements)

References 34 publications

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“…3-6 %) between SOD1 +/+ and SOD1 −/− mice at 5 weeks of age, suggesting that the immune system was not affected. It is known that oxidation leads to an increase in the antigenicity of erythrocytes when injected into peritonea [42]. Collectively, these findings suggest that oxidation-enhanced antigenicity of erythrocytes and accelerated destruction of oxidized erythrocytes co-ordinately caused autoantibody production in SOD1 −/− mice.…”

Section: Discussionmentioning

confidence: 73%

Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production

Iuchi

Okada

Onuma

et al. 2007

Biochemical Journal

149

105

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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.

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Section: Discussionmentioning

confidence: 73%

Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production

Iuchi

Okada

Onuma

et al. 2007

Biochemical Journal

149

105

View full text Add to dashboard Cite

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“…Erythrocytes that matured from reticulocytes produced during conditions of severe erythropoietic stress also had decreased half-lives compared to erythrocytes derived from reticulocytes produced under basal erythropoiesis or a milder erythropoietic stress (Stryckmans et al 1968). Similar to reticulocytes, iron-deficient mature RBCs had the shortest life span of all and demonstrated increased susceptibility to intravascular and extravascular hemolysis (Signorini et al 1995) resulting in a 15-fold decreased life span in circulation compared to RBCs maturing from iron-replete stress reticulocytes (Robinson and Koeppel 1971;Wiczling, Ait-Oudhia, and Krzyzanski 2009). The prothrombotic consequence of turning over significant numbers of reticulocyte/RBCs can be related to the mechanism of their removal.…”

Section: Discussionmentioning

confidence: 99%

Dose-related Differences in the Pharmacodynamic and Toxicologic Response to a Novel Hyperglycosylated Analog of Recombinant Human Erythropoietin in Sprague-Dawley Rats with Similarly High Hematocrit

et al. 2013

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We recently reported results that erythropoiesis-stimulating agent (ESA)-related thrombotic toxicities in preclinical species were not solely dependent on a high hematocrit (HCT) but also associated with increased ESA dose level, dose frequency, and dosing duration. In this article, we conclude that sequelae of an increased magnitude of ESA-stimulated erythropoiesis potentially contributed to thrombosis in the highest ESA dose groups. The results were obtained from two investigative studies we conducted in Sprague-Dawley rats administered a low (no thrombotic toxicities) or high (with thrombotic toxicities) dose level of a hyperglycosylated analog of recombinant human erythropoietin (AMG 114), 3 times weekly for up to 9 days or for 1 month. Despite similarly increased HCT at both dose levels, animals in the high-dose group had an increased magnitude of erythropoiesis measured by spleen weights, splenic erythropoiesis, and circulating reticulocytes. Resulting prothrombotic risk factors identified predominantly or uniquely in the high-dose group were higher numbers of immature reticulocytes and nucleated red blood cells in circulation, severe functional iron deficiency, and increased intravascular destruction of iron-deficient reticulocyte/red blood cells. No thrombotic events were detected in rats dosed up to 9 days suggesting a sustained high HCT is a requisite cofactor for development of ESA-related thrombotic toxicities.

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“…The possible reason of hemolysis may be due to damage to the membrane components due to oxidative stress leading to haemoglobin leakage. Some workers have also reported similar observations in the erythrocytes releasing hemoglobin in the vasculature during ageing [25][26]. Studies related to measurement of osmotic fragility of erythrocytes exposed to oxidative stress indicated a decrease as the concentration of the system increases.…”

Section: Antioxidant Enzymesmentioning

confidence: 53%

Effect of Free Radical Generating System- Adenosine Triphosphate/Ferrous Sulphate/Hydrogen Peroxide on Human Erythrocytes

Punjabi¹,

Gokhale²

2017

ijcrr

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Abstract:Erythrocytes constitute the major cell fraction of blood in the body continuously exposed to oxygen in vivo and hence liable to undergo oxidative damage like lipid oxidation and protein denaturation thereby affecting their function. The aim of the present work is to create an analogous oxidative environment for human erythrocytes in vitro using free radical generating system-ATP/FeSO4/H2O2 and to study its effect on their properties. It has been found that erythrocytes undergo hemolysis during exposure to oxidative stress at the same time cells become resistant to osmotic fragility after treatment. The membranes isolated from treated cells show additional bands corresponding to cytosolic proteins on electrophoretic gel. Decreased erythrocyte superoxide dismutase and catalase levels were observed in the cells exposed to ATP/FeSO4/H2O2. It is concluded that excessive oxidative environment results in alterations of the cellular systems.Keywords: erythrocyte; oxidative stress; adenosine triphosphate; hemolysis; protein modification; antioxidant enzymes Introduction:

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Iron release, membrane protein oxidation and erythrocyte ageing

Cited by 69 publications

References 34 publications

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

Dose-related Differences in the Pharmacodynamic and Toxicologic Response to a Novel Hyperglycosylated Analog of Recombinant Human Erythropoietin in Sprague-Dawley Rats with Similarly High Hematocrit

Effect of Free Radical Generating System- Adenosine Triphosphate/Ferrous Sulphate/Hydrogen Peroxide on Human Erythrocytes

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