Hypoxic regulation of erythropoiesis and iron metabolism

Department of Medicine, Vanderbilt School of Medicine, Nashville, Tennessee 37232, USA.
AJP Renal Physiology (Impact Factor: 3.25). 07/2010; 299(1):F1-13. DOI: 10.1152/ajprenal.00174.2010
Source: PubMed


The kidney is a highly sensitive oxygen sensor and plays a central role in mediating the hypoxic induction of red blood cell production. Efforts to understand the molecular basis of oxygen-regulated erythropoiesis have led to the identification of erythropoietin (EPO), which is essential for normal erythropoiesis and to the purification of hypoxia-inducible factor (HIF), the transcription factor that regulates EPO synthesis and mediates cellular adaptation to hypoxia. Recent insights into the molecular mechanisms that control and integrate cellular and systemic erythropoiesis-promoting hypoxia responses and their potential as a therapeutic target for the treatment of renal anemia are discussed in this review.

Full-text preview

Available from:
  • Source
    • "Recently, it was shown that NF-κB (nuclear factor κB) is a modulator of HIF 2 expression in the presence of normal oxygen pressure (Haase et al., 2010, Willam, 2014). NF-κB indirectly controls HIF 2α through its control of HIF 1β (van Uden et al., 2011). "

    Critical reviews in food science and nutrition 07/2015; DOI:10.1080/10408398.2015.1050483 · 5.18 Impact Factor
  • Source
    • "However, this could not be confirmed in the isolated hepatocytes [93], and other indirect pathways by which HIF regulates hepcidin expression may exist. It has been found that HIF could regulate renal and hepatic EPO synthesis directly under hypoxia [94], and the activation of hepatic HIF itself without the concomitant increase in EPO transcription did not suppress hepcidin expression [95]. Therefore, the regulation of HIF on hepcidin may be mediated by affecting the EPO synthesis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Iron is an important mineral element used by the body in a variety of metabolic and physiologic processes. These processes are highly active when the body is undergoing physical exercises. Prevalence of exercise-induced iron deficiency anemia (also known as sports anemia) is notably high in athletic populations, particularly those with heavy training loads. The pathogenesis of sports anemia is closely related to disorders of iron metabolism, and a more comprehensive understanding of the mechanism of iron metabolism in the course of physical exercises could expand ways of treatment and prevention of sports anemia. In recent years, there have been remarkable research advances regarding the molecular mechanisms underlying changes of iron metabolism in response to physical exercises. This review has covered these advances, including effects of exercise on duodenum iron absorption, serum iron status, iron distribution in organs, erythropoiesis, and hepcidin's function and its regulation. New methods for the treatment of exercise-induced iron deficiency are also discussed.
    Cell and Bioscience 04/2014; 4(1):19. DOI:10.1186/2045-3701-4-19 · 3.63 Impact Factor
  • Source
    • "Upon stabilization, alpha subunits enter the nucleus, where they dimerize with HIF-β. The dimer binds to a specific base sequence in the promoter region of genes called hypoxia response element, HRE, to induce the expression of genes (for recent reviews see (Semenza, 2009; Haase, 2010)). Besides stabilization, HIF-alpha subunits are also controlled at the transcriptional level (Görlach, 2009; Semenza, 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: During exercise the cardiovascular system has to warrant substrate supply to working muscle. The main function of red blood cells in exercise is the transport of O2 from the lungs to the tissues and the delivery of metabolically produced CO2 to the lungs for expiration. Hemoglobin also contributes to the blood's buffering capacity, and ATP and NO release from red blood cells contributes to vasodilation and improved blood flow to working muscle. These functions require adequate amounts of red blood cells in circulation. Trained athletes, particularly in endurance sports, have a decreased hematocrit, which is sometimes called "sports anemia." This is not anemia in a clinical sense, because athletes have in fact an increased total mass of red blood cells and hemoglobin in circulation relative to sedentary individuals. The slight decrease in hematocrit by training is brought about by an increased plasma volume (PV). The mechanisms that increase total red blood cell mass by training are not understood fully. Despite stimulated erythropoiesis, exercise can decrease the red blood cell mass by intravascular hemolysis mainly of senescent red blood cells, which is caused by mechanical rupture when red blood cells pass through capillaries in contracting muscles, and by compression of red cells e.g., in foot soles during running or in hand palms in weightlifters. Together, these adjustments cause a decrease in the average age of the population of circulating red blood cells in trained athletes. These younger red cells are characterized by improved oxygen release and deformability, both of which also improve tissue oxygen supply during exercise.
    Frontiers in Physiology 11/2013; 4:332. DOI:10.3389/fphys.2013.00332 · 3.53 Impact Factor
Show more