Mechanism of induction of haemolytic anaemia by phenylhydrazine

Itano, Harvey A.; Hirota, Kazuhiro; Hosokawa, Keimei

doi:10.1038/256665a0

Cited by 62 publications

(41 citation statements)

References 15 publications

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“…Ϫ/Ϫ Mice-Phenylhydrazine (PHZ), a potent inducer of oxidative stress in vivo, is capable of denaturing hemoglobin and hemolyzing red cells (32). To test PHZ tolerance, we injected wild-type and AMPK␣1 Ϫ/Ϫ mice with 100 mg/kg PHZ.…”

Section: Phenylhydrazine-induced Mortality Is Increased In Ampk␣1mentioning

confidence: 99%

AMPKα1 Deletion Shortens Erythrocyte Life Span in Mice

Wang

Dale

Song

et al. 2010

Journal of Biological Chemistry

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Section: Phenylhydrazine-induced Mortality Is Increased In Ampk␣1mentioning

confidence: 99%

AMPKα1 Deletion Shortens Erythrocyte Life Span in Mice

Wang

Dale

Song

et al. 2010

Journal of Biological Chemistry

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“…To monitor the effect of hemin addition on intact reticulocytes in wild-type and Gadd34-null mice, we enriched the blood cell population for reticulocytes with phenylhydrazine. Phenylhydrazine enrichment results in the peroxidation and ultimate hemolysis of mature erythrocytes, thus stimulating the production of reticulocytes in the bone marrow and ultimately their release into the bloodstream (12). After hemin addition, wild-type erythrocytes show a modest reduction in levels of p-eIF2␣(S51), while the Gadd34-null reticulocytes maintain substantial and constitutive p-eIF2␣(S51) levels (Fig.…”

Section: Vol 26 2006mentioning

confidence: 99%

Gadd34 Requirement for Normal Hemoglobin Synthesis

Patterson

Hollander

Miller

et al. 2006

Molecular and Cellular Biology

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The protein encoded by growth arrest and DNA damage-inducible transcript 34 (Gadd34) is associated with translation initiation regulation following certain stress responses. Through interaction with the protein phosphatase 1 catalytic subunit (PP1c), Gadd34 recruits PP1c for the removal of an inhibitory phosphate group on the ␣ subunit of elongation initiation factor 2, thereby reversing the shutoff of protein synthesis initiated by stress-inducible kinases. In the absence of stress, the physiologic consequences of Gadd34 function are not known. Initial analysis of Gadd34-null mice revealed several significant findings, including hypersplenism, decreased erythrocyte volume, increased numbers of circulating erythrocytes, and decreased hemoglobin content, resembling some thalassemia syndromes. Biochemical analysis of the hemoglobin-producing reticulocyte (an erythrocyte precursor) revealed that the decreased hemoglobin content in the Gadd34-null erythrocyte is due to the reduced initiation of the globin translation machinery. We propose that an equilibrium state exists between Gadd34/PP1c and the opposing heme-regulated inhibitor kinase during hemoglobin synthesis in the reticulocyte.

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“…PHZ is widely used to induce hemolysis because it provokes denaturation of oxyhemoglobin, accumulation of Heinz bodies in erythrocytes, and damage of cells (47). The damaged rbc are mostly engulfed by macrophages in the spleen and liver.…”

Section: Figurementioning

confidence: 99%

The function of heme-regulated eIF2α kinase in murine iron homeostasis and macrophage maturation

Liu¹,

Suragani²,

Wang³

et al. 2007

J. Clin. Invest.

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Heme-regulated eIF2α kinase (HRI) plays an essential protective role in anemias of iron deficiency, erythroid protoporphyria, and β-thalassemia. In this study, we report that HRI protein is present in murine macrophages, albeit at a lower level than in erythroid precursors. Hri -/-mice exhibited impaired macrophage maturation and a weaker antiinflammatory response with reduced cytokine production upon LPS challenge. The level of production of hepcidin, an important player in the pathogenesis of the anemia of inflammation, was significantly decreased in Hri -/-mice, accompanied by decreased splenic macrophage iron content and increased serum iron content. Hepcidin expression was also significantly lower, with a concomitant increase in serum iron in Hri -/-mice upon LPS treatment. We also demonstrated an impairment of erythrophagocytosis by Hri -/-macrophages both in vitro and in vivo under chronic hemolytic anemia, providing evidence for the role of HRI in recycling iron from senescent red blood cells. This work demonstrates that HRI deficiency attenuates hepcidin expression and iron homeostasis in mice, indicating a potential role for HRI in the anemia of inflammation.

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Mechanism of induction of haemolytic anaemia by phenylhydrazine

Cited by 62 publications

References 15 publications

AMPKα1 Deletion Shortens Erythrocyte Life Span in Mice

AMPKα1 Deletion Shortens Erythrocyte Life Span in Mice

Gadd34 Requirement for Normal Hemoglobin Synthesis

The function of heme-regulated eIF2α kinase in murine iron homeostasis and macrophage maturation

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