The regulation of erythropoiesis by selenium in mice.

Abstract

Redox modulation by antioxidants, such as selenium (Se), has emerged as an important regulator of erythropoiesis. Using Se-deficient (0.04 ppm), Se-adequate (0.1 ppm), and Se-supplemented (0.4 ppm) C57/BL6 mice, we show that Se deficiency caused anemia, when compared to the Se-supplemented and Se-adequate groups. Increased denaturation of hemoglobin, methemoglobin, protein carbonyls, lipid peroxidation, Heinz bodies, and osmotic fragility of erythrocytes were observed in Se-deficient mice. Increased oxidative stress upregulated forkhead transcription factor (FoxO3a) and hypoxia-inducible factor-(HIF)1α in the spleen and kidney of Se-deficient murine as well as in the proerythroblast G1E cells cultured in Se-deficient media. A significant increase in the expression of erythropoietin, a downstream target of HIF1α, and expansion of stress erythroid progenitors (burst forming units-erythroid) were seen in the Se-deficient mice. Despite the increase in erythroid progenitors, lowered reticulocytes suggest a defective erythroid differentiation pathway. While Se deficiency led to increased nuclear levels of active FoxO3a, Se-adequate conditions reversed this effect and increased nuclear export by its binding partner, 14-3-3βζ, that is under the redox control of selenoproteins. In summary, these results provide insight into the importance of adequate Se nutrition in regulating red cell homeostasis by mitigating oxidative stress-dependent modulation of FoxO3a and HIF1α to effect differentiation of erythroid progenitors.

• Authors: Naveen Kaushal, Shailaja Hegde, Jeanne Lumadue, Robert F Paulson, K Sandeep Prabhu
• Journal: Antioxidants & redox signaling (Antioxid Redox Signal) Vol. 14 Issue 8 Pg. 1403-12 (Apr 15 2011) ISSN: 1557-7716 [Electronic] United States
• PMID: 20969477 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antioxidants
• Forkhead Box Protein O3
• Forkhead Transcription Factors
• FoxO3 protein, mouse
• Hif1a protein, mouse
• Hypoxia-Inducible Factor 1, alpha Subunit
• Selenium

Topics

• Animals
• Antioxidants (pharmacology)
• Cells, Cultured
• Dietary Supplements
• Erythrocytes (drug effects, metabolism)
• Erythropoiesis (drug effects)
• Forkhead Box Protein O3
• Forkhead Transcription Factors (metabolism)
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Mice
• Mice, Inbred C57BL
• Oxidation-Reduction
• Oxidative Stress
• Selenium (administration & dosage, deficiency, pharmacology)