The effect of hypoxia and stem cell source on haemoglobin switching

Narayan, Alison R. H.; Ersek, Adel; Campbell, Thomas A.; Colon, Donna M.; Pixley, John S.; Zanjani, Esmail D.

doi:10.1111/j.1365-2141.2004.05336.x

Cited by 21 publications

(19 citation statements)

References 31 publications

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“…26 However, no hormonal trigger has been identified to date for the fetal-to-adult switch in humans or other mammals. Results from sheep, 27 primates, 28 and humans 29,30 suggest that signal transduction does play a role in the regulation of the gamma-globin gene in adults. In the laboratory, pancellular expression of the gammaglobin gene is achievable via signal transduction by specific cytokines.…”

Section: Discussionmentioning

confidence: 99%

Fetal hemoglobin silencing in humans

O'Neal

Gantt

Schwartz

et al. 2006

Blood

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Interruption of the normal fetal-to-adult transition of hemoglobin expression should largely ameliorate sickle cell and beta-thalassemia syndromes. Achievement of this clinical goal requires a robust understanding of gamma-globin gene and protein silencing during human development. For this purpose, age-related changes in globin phenotypes of circulating human erythroid cells were examined from 5 umbilical cords, 99 infants, and 5 adult donors. Unexpectedly, an average of 95% of the cord blood erythrocytes and reticulocytes expressed HbA and the adult beta-globin gene, as well as HbF and the gamma-globin genes. The distribution of hemoglobin and globin gene expression then changed abruptly due to the expansion of cells lacking HbF or gamma-globin mRNA (silenced cells). In adult reticulocytes, less than 5% expressed gamma-globin mRNA. These data are consistent with a "switching" model in humans that initially results largely from gamma-and beta-globin gene coexpression and competition during fetal development. In contrast, early postnatal life is marked by the rapid accumulation of cells that possess undetectable gamma-globin mRNA and HbF. The silencing phenomenon is mediated by a mechanism of cellular replacement. This novel silencing pattern may be important for the development of HbF-enhancing thera-

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Section: Discussionmentioning

confidence: 99%

Fetal hemoglobin silencing in humans

O'Neal

Gantt

Schwartz

et al. 2006

Blood

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“…Interestingly, hypoxia has been recently demonstrated to alter progression of the erythroid program (29). Low pO2 might indeed modulate the relative amounts and types of hemoglobins produced by erythroid cells, leading to increased HbF during stress erythropoiesis (29)(30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Expression of miR-210 during erythroid differentiation and induction of γ-globin gene expression

Bianchi¹,

Zuccato²,

Lampronti³

et al. 2009

BMB Reports

113

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“…However, a large variation was observed and the difference was not significant The early stage of PE development is characterized by uneven and insufficient perfusion of the placenta leading to hypoxia [3,38]. Hypoxia has been reported to increase erythropoiesis, via HIF-1-induced synthesis of erythropoietin (reviewed in [39]), and induce a switch from HbA to HbF in cord blood cells and bone marrow cells [40,41]. Thus, the upregulation of HbF gene expression and placental HbF accumulation reported by Centlow et al…”

Section: In Placentamentioning

confidence: 99%

Increased levels of cell-free hemoglobin, oxidation markers, and the antioxidative heme scavenger α1-microglobulin in preeclampsia

Olsson

Centlow

Rutardóttir

et al. 2010

Free Radical Biology and Medicine

102

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Preeclampsia is a major cause of morbidity and mortality during pregnancy. To date, the pathogenesis of the disease is not fully understood. Recent studies show that preeclampsia is associated with overexpression of hemoglobin genes α2 and γ and accumulation of the protein in the vascular lumen of the placenta. Hypothesizing that cell-free hemoglobin leaks from the placenta into the maternal circulation and contributes to the endothelial damage and symptoms by inducing oxidative stress, we analysed fetal and adult hemoglobin (HbF, HbA), haptoglobin, oxidation markers and the heme scavenger and antioxidant α 1 -microglobulin in plasma, urine and placenta in preeclamptic women (n=28) and normal pregnancies (n=27).The mean plasma concentrations of HbF, HbA, protein carbonyl groups, membrane peroxidation capacity and α 1 -microglobulin were significantly increased in preeclamptic women. The levels of total plasma Hb correlated strongly with the systolic blood pressure.The plasma haptoglobin concentrations of women with preeclampsia were significantly depressed. Increased amounts of α 1 -microglobulin-mRNA and protein were found in placenta from preeclamptic women and the levels of plasma and placenta α 1 -microglobulin correlated to plasma Hb-concentrations. The heme-degrading form t-α 1 -microglobulin was significantly increased in urine in preeclampsia. These results support that hemoglobin-induced oxidative stress is a pathogenic factor in preeclampsia.

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The effect of hypoxia and stem cell source on haemoglobin switching

Cited by 21 publications

References 31 publications

Fetal hemoglobin silencing in humans

Fetal hemoglobin silencing in humans

Expression of miR-210 during erythroid differentiation and induction of γ-globin gene expression

Increased levels of cell-free hemoglobin, oxidation markers, and the antioxidative heme scavenger α1-microglobulin in preeclampsia

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