Cellular Zinc Deficiency Impairs Heme Biosynthesis in Developing Erythroid Progenitors

Abstract

Anemia is the most prevalent nutrition-related disorder worldwide. Zinc is an essential trace element for various biological processes in the body, and zinc deficiency has been associated with anemia in humans. However, the molecular mechanisms by which zinc availability alters red blood cell development remain uncertain. The present study identifies the essentiality of zinc during erythroid development, particularly for normal heme biosynthesis. G1E-ER4 mouse cells were used as an in vitro model of terminal erythroid differentiation, which featured elevated cellular zinc content by development. Restriction of zinc import compromised the rate of heme and α-globin production and, thus, the hemoglobinization of the erythroid progenitors. Heme is synthesized by the incorporation of iron into protoporphyrin. The lower heme production under zinc restriction was not due to changes in iron but was attributable to less porphyrin synthesis. The requirement of adequate zinc for erythroid heme metabolism was confirmed in another erythropoietic cell model, MEL-DS19. Additionally, we found that a conventional marker of iron deficiency anemia, the ZnPP-to-heme ratio, responded to zinc restriction differently from iron deficiency. Collectively, our findings define zinc as an essential nutrient integral to erythroid heme biosynthesis and, thus, a potential therapeutic target for treating anemia and other erythrocyte-related disorders.

The Effectiveness of The Use of Macrolide Antibiotic in Infectious Diseases

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Modulation of the Adverse Health Effects of Environmental Cadmium Exposure by Zinc and Its Transporters

“…Because δ-aminolevulinic acid dehydratase (ALD), an enzyme in heme biosynthesis is Zndependent, anemia in Zn deficiency conditions was due to insufficient amount of heme for hemoglobin synthesis [104]. A methodological breakthrough in measuring bilirubin in cells was made, following a discovery of a protein capable of binding unconjugated bilirubin [105].…”

Modulation of Adverse Health Effects of Environmental Cadmium Exposure by Zinc and Its Transporters

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