Fig. 1: Identification of JQ-1 as the candidate compound for the inhibition of cardiomyocyte ferroptosis.

A Screening strategy for small molecular from epigenetic compounds library in H9C2 cardiomyocytes. B Scatter plot of the effect of small molecule compounds in the library on erastin-induced cellular viability in H9C2 cardiomyocytes. Green dots [Log₂(Fold change) > 4] indicate anti-ferroptosis candidate compounds, blue dots [Log₂(Fold change) < 0] indicate pro-ferroptosis candidate compounds, gray dots [0≦Log₂(Fold change) ≦4] indicate compounds that have no effect on ferroptosis. C Effect of JQ-1 (1 μM) on the cell viability in H9C2 cardiomyocytes (up) and neonatal rat ventricular myocytes (NRVMs, down) treated with erastin (2.5 μM). The positive control was represented by the use of Fer-1 (2 μM) (n = 5–6). D The representative images of bright field (BF), Calcein-AM, and propidium iodide (PI) staining in H9C2 cardiomyocytes treated with JQ-1 under the erastin challenge. Green indicates the fluorescence of Calcein-AM, red indicates the fluorescence of PI. Scale bars, 100 µm, (n = 6). E The relative mRNA levels of Ptgs2 and Homx1 in JQ-1-treated H9C2 cardiomyocytes under the erastin challenge (n = 4). F Western blot analysis was conducted to assess the expression of FPN, SLC7A11, and GPX4 in JQ-1-treated H9C2 cardiomyocytes under the erastin challenge. G The relative protein levels of FPN, SLC7A11, and GPX4 were quantified in (F) (n = 4). The data are presented as mean ± SEM. The statistical significance of the data was evaluated using a two-way ANOVA followed by Tukey’s test for multiple comparisons (C, E, and G). *P < 0.05; **P < 0.01.