Fig. 4

Afatinib, sorafenib and ponatinib induce ER stress in NRCMs and rat hearts. A Fold changes of ER stress related genes, Atf4 and its targets, Chac1, Ddit3, Trib3;Xbp1s, and its target Dnajb9; Atf6 and its targets Hspa5 and Herpud1, in NRCMs treated with afatinib at 5.62 or 10 µM for 24 h. B Fold changes of ER stress related genes in NRVMs treated with sorafenib at 3.16 or 10 µM for 24 h. C Fold changes of ER stress related genes in NRCMs treated with ponatinib at 1.78 or 5.62 µM for 24 h. D Left: heatmap of gene expression changes from A–C. Right: heatmap of gene expression changes caused by afatinib 5.62 µM, sorafenib 3.16 µM, or ponatinib 1.78 µM at 24 or 72 h. E Phospho-eIF2α (or EIF2S1), XBP1s, ATF6 (cleaved), and GAPDH expression at different time points under afatinib, sorafenib, and ponatinib treatment measured by Western blot. F–H Fold changes of Anp, Dnajb9, and Ddit3 in rat left ventricles from sorafenib or ponatinib gavage for 3 or 7 days. A-C Data were presented as mean ± SEM (n = 3) and analyzed using ANOVA analysis. *p < 0.05, **p < 0.01, ***p < 0.001 versus the DMSO vehicle control group. ^#p < 0.05, ^##p < 0.01, ^###p < 0.001 versus the lower dose. F–H Data were presented as mean ± SEM (n = 8) and analyzed using ANOVA analysis. *p < 0.05, **p < 0.01, ***p < 0.001 versus the vehicle control