Journal: Communications Biology

Article Title: Activation of the urotensin-II receptor by remdesivir induces cardiomyocyte dysfunction

doi: 10.1038/s42003-023-04888-x

Figure Lengend Snippet: a Serum-starved HEK293 cells overexpressing UTS2R were stimulated with the indicated concentrations of remdesivir for 5 min with or without urantide, a UTS2R antagonist, and the lysates subjected to western blotting analysis. ERK1 and ERK2 activation ratios (pERK1/ERK1 and pERK2/ERK2) were calculated with data normalized to the vehicle. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001 by Tukey’s multiple comparisons test. Data are represented as means ± SEM ( n = 3). b Left, Temporal correlation between the field potential duration and the QT interval on the surface ECG. Right, Schematic of the multielectrode array (MEA) platform. c Representative field potential waveform in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) treated with 1 µM remdesivir in the presence or absence of urantide for 72 h. d Effect of remdesivir and urantide on field potential prolongation in hiPSC-CMs. * p < 0.05, ** p < 0.01 by two-way ANOVA followed by Šídák’s multiple comparisons tests. Data are represented as means ± SEM ( n = 3). e Perforated patch-clamp to record spontaneous action potentials of hiPS-CMs in current-clamp models. The hiPSC-CMs were treated with 10 µM remdesivir in the presence or absence of 50 µM urantide for 72 h. * p < 0.05 and ** p < 0.01 by Tukey’s multiple comparisons test. Data are represented as means ± SEM ( n ≥ 3).

Article Snippet: Right, Schematic of the multielectrode array (MEA) platform. c Representative field potential waveform in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) treated with 1 µM remdesivir in the presence or absence of urantide for 72 h. d Effect of remdesivir and urantide on field potential prolongation in hiPSC-CMs.

Techniques: Western Blot, Activation Assay, Derivative Assay, Patch Clamp

Journal: Communications Biology

Article Title: Activation of the urotensin-II receptor by remdesivir induces cardiomyocyte dysfunction

doi: 10.1038/s42003-023-04888-x

Figure Lengend Snippet: a , b Left, Representative waveform of contractility under pacing in neonatal rat cardiomyocytes (NRCMs) by 1 µM remdesivir with or without a urantide or b pertussis toxin (PTX), a Gα i/o inhibitor, and YM-254890, a Gα q/11 inhibitor, at 48 h. Right, the effect of remdesivir with a urantide or b PTX and YM-254890 on contractility under pacing in NRCMs. ** p < 0.01, *** p < 0.001, **** p < 0.0001 by Tukey’s multiple comparisons test. Data are represented as means ± SEM ( n = 3). c , d Representative western blot for phosphorylation of c ERK1/2 and d protein kinase B (AKT). Serum-starved HEK293 cells overexpressing UTS2R were stimulated with the indicated concentrations of remdesivir for 48 h. For G i/o protein inhibition, cells were incubated with PTX for at least 18 h at 150 ng/mL. ERK1, ERK2, and AKT activation ratios were calculated with data normalized to the vehicle. * p < 0.05, ** p < 0.01, *** p < 0.001 by Tukey’s multiple comparisons test. Data are shown as means ± SEM ( n = 3). e , f The effects of remdesivir on the contractility of adult mouse cardiomyocytes. Isolated adult mouse cardiomyocytes were treated with remdesivir (10 µM) for 30 min, and the percentile change in cell area ( e ) and the ratio of cardiomyocyte shortening ( f ) was measured during electrical pacing. **** p < 0.001 by unpaired t -test. Data are shown as means ± SEM (a total of 54 cells from 3 mice).

Article Snippet: Right, Schematic of the multielectrode array (MEA) platform. c Representative field potential waveform in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) treated with 1 µM remdesivir in the presence or absence of urantide for 72 h. d Effect of remdesivir and urantide on field potential prolongation in hiPSC-CMs.

Techniques: Western Blot, Inhibition, Incubation, Activation Assay, Isolation