Redox Signaling in Sickle Cell Disease
2019
Sickle cell disease (SCD) is characterized by chronic hemolysis and repeated episodes of vascular occlusion leading to progressive organ injury. A dominant pathologic feature of SCD is the unbalanced, simultaneous pro-oxidant, and anti-oxidant processes at the molecular, cellular, and tissue levels, with the majority of reactions tipped in favor of pro-oxidant pathways. In this brief review, we discuss new findings regarding how oxidized hemin, hemolysis, mitochondrial dysfunction, and the innate immune system generate oxidative stress while hemopexin, haptoglobin, heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) may provide protection in human and murine SCD. We will also describe recent clinical trials showing beneficial effects of antioxidant therapy in SCD.
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