Investigation of the role of heme oxygenase-1 in β-thalassemia pathophysiology

Abstract

β -thalassemia is an inherited disorder characterized by impaired hemoglobin synthesis in developing erythrocytes due to unbalanced globin chain production, resulting in severe oxidative damage to cells. Heme oxygenase-1 (HO-1) has been shown to have antioxidant benefits and is upregulated in response to oxidative stress; thus increased HO-1 levels could serve as an indicator of β-thalassemia pathophysiology. To test this hypothesis, we created a cell culture model of β-thalassemia by decreasing β globin expression in murine erythroleukemic (MEL) cells using short interfering RNA (siRNA). An increase in HO-1 protein expression, along with a decrease in heme levels was observed in cells where β globin reduction was sustained for 96 hours. Further investigation is needed to determine the role that HO-1 plays in normal erythroid development and confirm the observed relationship between β globin reduction and increased HO-1 expression, however, our results provide evidence that this method serves as an effective and novel cell model of β thalassemia.