Defect in Stress Erythropoiesis during Selenium Deficiency

Abstract

Redox homeostasis occupies a pivotal role during stress erythropoiesis, but the key players and mechanisms are not well understood. We hypothesized that selenium (Se), well recognized for its redox properties, regulates stress erythroid progenitors, in part through stabilizing hemoglobin and efficient erythrocyte replenishment. Here we report preliminary findings in a classical model of phenyl hydrazine (PHZ)‐induced hemolytic anemia in mice fed diets deficient in Se (<0.01 ppm; Se‐D) or adequate in Se (0.08 ppm; Se‐A). Se‐D mice displayed poor survivability upon PHZ treatment with severe hemolysis and low hematocrit; while mice on Se‐A diet recovered from PHZ treatment within 10 days. In response to anemia, erythropoiesis occurs in the murine spleen. Se‐A mice rapidly expanded stress erythroid progenitors (BFU‐E; Burst forming unit‐ erythroid) during the first 3 days of recovery. In contrast Se‐D mice were unable to expand progenitors. In addition,qPCR analysis of the spleen showed that Se‐D mice failed to upregulate α‐hemoglobin stabilizing protein (AHSP), supporting defects in hemoglobin formation. Interestingly, Hsp70 was greatly upregulated in Se‐D mice, suggesting a compensatory mechanism of α‐hemoglobin chaperoning. These studies suggest that Se plays an important role in protection from hemolytic anemia by affecting expansion of erythroid progenitors in addition to enhancing the formation of stable hemoglobin molecules. Supported by grants from the National Institutes of Health to KSP and RFP