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. 2022 Mar 8;130(7):963–977. doi: 10.1161/CIRCRESAHA.121.320518

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© 2022 American Heart Association, Inc.

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Figure 7. — Deferoxamine and imatinib inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection–induced ferroptosis. A, Quantitative real-time polymerase chain reaction analysis of GPX4 expression levels in dimethyl sulfoxide (DMSO), 50 μM deferoxamine-treated, or 10 μM imatinib-treated human embryonic stem cell (hESC)–sinoatrial node (SAN)–like pacemaker cells at 24 hours postinfection (hpi) with SARS-CoV-2 (multiplicity of infection [MOI]=0.1). The graph represents the RNA level normalized to ACTB. B and C, Immunostaining (B) and quantification (C) of GPX4 expression levels in DMSO, 50 μM deferoxamine-treated, or 10 μM imatinib-treated hESC-SAN–like pacemaker cells at 24 hpi with SARS-CoV-2 (MOI=0.1). Scale bar=50 μm. D and E, Immunostaining (D) and quantification (E) of reactive oxygen species (ROS) in DMSO, 50 μM deferoxamine-treated, or 10 μM imatinib-treated hESC-SAN–like pacemaker cells at 24 hpi with SARS-CoV-2 (MOI=0.1). Scale bar=50 μm. F and G, Principal component (PC) analysis plot (F) and cluster analysis (G) of gene expression profiles of mock and DMSO, 50 μM deferoxamine-treated, or 10 μM imatinib-treated hESC-SAN–like pacemaker cells at 24 hpi with SARS-CoV-2 (MOI=0.1). H and I, Heatmap of ferroptosis-associated gene expression levels in DMSO, 50 μM deferoxamine-treated, or 10 μM imatinib-treated hESC-SAN–like pacemaker cells at 24 hpi with SARS-CoV-2 (MOI=0.1). The high Z score indicates high gene expression level. N=3 independent experiments. Data are presented as mean±SD. DAPI indicates 4′,6-diamidino-2-phenylindole; GPX, glutathione peroxidase; MYH6: mCherry, myosin heavy chain 6: mcherry; and SHOX2:GFP, short stature homeobox 2: green fluorescent protein. P values were calculated by 1-way ANOVA with an indicated control. *P<0.05 and **P<0.01.