Fig. 1.

Effects of hemin administration on rate limiting enzymes of heme synthesis and catabolism. A) Regulation of heme synthesis and potential antiviral effect of hemin administration. The first and rate limiting step in heme synthesis is the conversion of glycine and succinyl-coenzyme A to form δ-aminolevulinic acid (ALA), catalyzed by ALA synthase-1 (ALAS1). Heme oxygenase-1 (HO-1) is the inducible isoform of HO responsible for the oxidative cleavage of heme groups to yield carbon monoxide (CO) and biliverdin, which is subsequently reduced to bilirubin by the cytosolic biliverdin reductase enzyme. CO is a strong vasodilatory, anti-inflammatory and immunomodulatory agent and both biliverdin reductase B and bilirubin are efficient scavengers of Reactive Oxygen Species (ROS) and reduce the formation of peroxidation products. Fold-change expression of HO-1 in B) Vero-E6 and C) Calu-3 cell lines was measured after exposure to 64.4 µM of hemin. Immunoblot analyses of HO-1 protein levels in D) Vero-E6 and E) Calu-3 cell lines treated with two hemin concentrations (21.5 μM and 64.4 μM) for 48 h. F) Fold change of ALAS1 expression after hemin exposure. Results were plotted as mean ± SD from three experiments. *** p < 0.001 vs untreated control condition.