Glutathione peroxidase 4 and vitamin E control reticulocyte maturation, stress erythropoiesis and iron homeostasis.

Bilirubin levels appeared to increase with the ablation of Gpx4 under both conditions (± vitamin E), but the standard deviation (SD) was high so that differences became barely significant ( Figure 6S-U ).

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Under combined Gpx4 - and vitamin E-deficiency plasma EPO and ERFE levels increased to very high and highly significant levels ( Figure 6P,Q ), apparently mirroring the severity of erythropenia under combined Gpx4 - and vitamin E-deficiency. 52 Taken together, the defect in reticulocyte maturation by loss of the Gpx4 gene causes ineffective erythropoiesis with simultaneous iron overload in the liver and iron-deficiency in the hematopoietic system and this phenotype is to a large part masked by vitamin E in the normal diet.

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