Genetic Silencing Of Keap1 Induces Nrf2 Mediated Oxidative Stress Pathway In Human Erythroid Cells

Sickle cell disease (SCD) is a monogenic hereditary disorder resulting from a mutation in the β-globin gene which renders the red blood cells (RBCs) prone to sickling and hemolysis. SCD is characterized by several severe pathophysiologies including anemia, chest pain, stroke and vaso-occlusive crisis (VOC). Hemolysis has been attributed as one of the major contributing factors to these pathologies and has been linked to oxidative stress in RBCs that carry high levels of pro-oxidant heme. Additionally, sickle RBCs have an increased rate of auto-oxidation cycle that results in production of superoxide. Other factors including deformation and subsequent physical stress on the membrane during transit through narrow capillaries aggravate lipid peroxidation mediated damage. Therapies that can improve the antioxidant status and overall RBC health may offer a protective effect in this disease.