Oxidation and erythropoiesis

Erythropoiesis is a complex multistep process going from committed erythroid progenitors to mature red cells. Although recent advances allow the characterization of some components of erythropoiesis, much still remains to be investigated particularly on stress erythropoiesis. This review summarizes recent progresses made to understand the impact of oxidative stress on normal and pathologic erythropoiesis.

During erythroid maturation, reactive oxygen species might function as second messenger through either transient oxidation of cysteine residues on signaling targets or modulation of intracellular signaling pathways. Thus, in erythropoiesis, efficient cytoprotective systems are required to limit possible reactive oxygen species-related toxic effects especially in stress erythropoiesis characterized by severe oxidation such as β-thalassemia. In addition, prolonged or severe oxidative stress impairs autophagy, which might contribute to the block of erythroid maturation in stress erythropoiesis. Understanding the functional role of cytoprotective systems such as peroxiredoxin-2 or classical molecular chaperones such as the heat shock proteins will contribute to develop innovative therapeutic strategies for ineffective erythropoiesis.

We provide an update on cytoprotective mechanisms against oxidation in normal and stress erythropoiesis. We discuss the role of oxidative sensors involved in modulation of intracellular signaling during erythroid maturation process in normal and stress erythropoiesis.