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Grant Abstract: Selenium, Selenoproteins, and Stress Erythropoiesis

Grant Number: 5R01DK119865-02
PI Name: Prabhu
Project Title: Selenium, Selenoproteins, and Stress Erythropoiesis

Abstract: Through this administrative supplement, we propose key experiments to compare the two commonly used forms of micronutrient selenium (Se), inorganic selenite and organic selenomethionine (SeMet), as dietary supplements in effectively promoting erythropoiesis in response to anemic stress. In human studies, low serum Se has been independently associated with anemia suggesting dietary Se along with iron may be important in treating anemia. The effect of dietary Se deficiency and importance of selenoproteins in stress erythropoiesis has been recently described by our laboratory; however, it is not clear from the proposed studies in the parent grant if the form of Se in the diet impacts the recovery from anemia. Here we propose to extend the study to examine the effects of two forms of Se in the form of inorganic selenite versus organic selenomethionine in the diet on intermediary stages during stress erythropoiesis. Studies will utilize flow-cytometric analysis in addition to other hemodynamic and biochemical parameters in mice where anemia is induced using phenylhydrazine or bone marrow transplantation. Furthermore, we will also undertake studies to delineate the importance of the form of Se via changes in selenoproteins and non-selenoproteins to understand the underlying mechanisms in specific progenitor cell types that likely depend on the form of Se to support key cellular programs to effectively regulate efficient stress erythropoiesis. Mice that lack selenoproteins (via deletion of tRNASec) will be used in these studies. Using the transcriptomic analysis of specific early and late progenitors, we will examine their effect on cell-specific transcriptomic signatures as potential biomarkers that are sensitive to the form of Se used.

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