Edwin Liu Rose Hills
Clarifying the Mechanisms of Ergothioneine Depletion in Sickle Cell Disease (SCD)
Sickle Cell Disease is a disorder in which a point mutation in the -globin gene causes a structurally unstable form of hemoglobin (HbS). This instability generates higher levels of superoxide and hydrogen peroxide that cause rapid oxidation of erythrocyte (Red Blood Cell) membranes, and subsequently promotes polymerization of HbS, forming the sickling in Sickle Cell Disease. The pro-oxidant effects of the HbS mutation lead to rapid hemolysis, blockage of microvasculature, and release of reactive agents that further cause peripheral tissue damage. HbS is more redox active and more prone to act as a heme peroxidase relative to regular hemoglobin, and our lab has hypothesized that Ergothioneine, an antioxidant, is preferentially depleted by hemoglobin peroxidase activity. To test this hypothesis, I will modulate cellular hemoglobin peroxidase activity and determine its effect on the oxidation on the major intracellular antioxidants ascorbate (Vitamin C), glutathione, and ergothioneine.