Effect of hemin on gene expression in erythroid progenitors derived from human sickle cell disease peripheral blood mononuclear cells (PBMC)

Sickle cell disease endured chronic hemolysis and systemic hypxic conditions. SCD patients have aberrant metabolic regulation of fumarate, glutamate, glycine, malate, and other metabolites involved in glycolysis, nucleotide catabolism, and glutathione metabolism. To investigate the effect of hemin on the erythroid progenitors (EPs) derived form SCD PBMC, the transcriptome of hemin treated SCD EPs were explored under hypxoic condition (1% O2). Meanwhile, to explore chemical compounds that can alleviate hemin effect,gene expression profiles of dimethyl alpha ketoglutarate (DMKG), dimethyl fumarate (DMF) were studied. We found that DMKG and DMF showed protection effect against hemin through inducing the expression of NRF2-mediated antioxidantive signaling. NRF2 activation induced cellular anti-ferroptosis response to increase the SCD EPs viability and proliferation. Our findings suggest DMF and DMKG could be explored as novel SCD treatment options.