The Regulation of Erythropoiesis by Selenium in Mice
The Regulation of Erythropoiesis by Selenium in Mice
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DOI：
10.1089/ars.2010.3323
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发表时间：
2011-04-01
影响因子：
6.6
通讯作者：
Prabhu, K. Sandeep
中科院分区：
文献类型：
--
作者：
Kaushal, Naveen;Hegde, Shailaja;Prabhu, K. Sandeep
氧化还原调节抗氧化剂，如硒（Se），已成为一个重要的调节红细胞生成。使用硒缺乏（0.04 ppm）、硒充足（0.1 ppm）和硒补充（0.4 ppm）的C57/BL6小鼠，我们发现与硒补充组和硒充足组相比，硒缺乏引起贫血。在缺硒小鼠中观察到血红蛋白、高铁血红蛋白、蛋白羰基、脂质过氧化、亨氏体和红细胞渗透脆性的变性增加。氧化应激的增加上调了缺硒小鼠脾脏和肾脏中的叉头转录因子（FoxO3a）和缺氧诱导因子-(HIF)1 α，以及在缺硒培养基中培养的红细胞原G1E细胞。在缺硒小鼠中，促红细胞生成素（HIF1 α的下游靶点）的表达显著增加，应激红细胞祖细胞（破裂形成单位-红细胞）的扩增。尽管红系祖细胞增多，但网状红细胞减少表明红系分化途径存在缺陷。硒缺乏导致活性FoxO3a的核水平增加，而硒充足的条件逆转了这一效应，并增加了其结合伙伴14-3-3 beta zeta的核输出，这是受硒蛋白氧化还原控制的。综上所述，这些结果揭示了充足的硒营养通过减轻氧化应激依赖性的FoxO3a和HIF1 α的调节来调节红细胞稳态的重要性，从而影响红细胞祖细胞的分化。Antioxid。氧化还原信号，14,1403-1412。
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)1 alpha in the spleen and kidney of Sedeficient 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 HIF1 alpha, 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, 14-3-3 beta zeta, 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 HIF1 alpha to effect differentiation of erythroid progenitors. Antioxid. Redox Signal. 14, 1403-1412.