Oxidative stress modulates heme synthesis and induces peroxiredoxin-2 as a novel cytoprotective response in β-thalassemic erythropoiesis

摘要: Background β-thalassemic syndromes are inherited red cell disorders characterized by severe ineffective erythropoiesis and increased levels of reactive oxygen species whose contribution to anemia is only partially understood. Design Methods We studied erythroid precursors from normal peripheral CD34+ cells in two-phase liquid culture proteomic, reverse transcriptase polymerase chain reaction immunoblot analyses. measured intracellular species, heme the activity δ-aminolevulinate-synthase-2. exposed K562 with silenced peroxiredoxin-2 H2O2 generated a recombinant for kinetic measurements presence or hemin. Results In β-thalassemia production was associated down-regulation oxygenase-1 biliverdin reductase up-regulation peroxiredoxin-2. agreement these observations we found decreased related significantly reduced first enzyme pathway, δ-aminolevulinate synthase-2 without differences its expression. demonstrated that inhibited both hemin as protective mechanism cells. then addressed question role exposing oxidative stress silencing human erythroleukemia expression up-regulated response required survive stress. showed binds high affinity, suggesting possible multifunctional cytoprotective β-thalassemia. Conclusions reduction might represent two novel stress-response systems.