Fig. 4.
The cardioprotective effect of SeMet depends on GPX4. (a) Representative HE staining of GPX4WT and GPX4KO mouse hearts (n = 4). Scale bar: 1000 μm. (b–d) Representative cardiac electrocardiographs of GPX4WT and GPX4KO mice. Ejection fraction (EF) and fractional shortening (FS) of the heart by electrocardiography (n = 4–6). (e) Kaplan‒Meier survival curves of the indicated mice treated with SeMet followed by DOX (20 mg/kg, i.p.). SeMet (0.75 mg/kg, by gavage, weekly) was administered before DOX administration and after the start of DOX (0.375 mg/kg, by gavage, weekly). (n = 7–10 mice per group). (f) Heatmap of significantly changed lipid species (PUFAs) (one-way ANOVA, FDR corrected p value < 0.05, n = 4 biologically independent samples) between two groups. Each row represents z score-normalized intensities of the detected lipid species. Each column represents a sample. The relative abundance of each lipid is color-coded, with red indicating high signal intensity and blue indicating low signal intensity. CE, cholesteryl ester; PE, phosphatidylethanolamine; PA, phosphatidic acid; PC, phosphatidylcholine; PG, phosphatidylglycerol; PI, phosphatidylinositol; PS, phosphatidylserine; FA, free fatty acid; TAG, triacylglycerol; DAG, diacylglycerol. (g–n) Levels of selected PUFAs with the indicated treatment. Data show the mean ± s.d. (*P < 0.05; **P < 0.01), n = 4. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)