Additional file 1 of Three tyrosine kinase inhibitors cause cardiotoxicity by inducing endoplasmic reticulum stress and inflammation in cardiomyocytes

Additional file 1: Table S1. An introduction to the pharmacology and toxicology of TKI drugs of different cardiotoxicity levels. Table S2. Endoplasmic reticulum stress gene markers under different conditions of sorafenib. Table S3. The ARRIVE checklist

Additional file 5 of Three tyrosine kinase inhibitors cause cardiotoxicity by inducing endoplasmic reticulum stress and inflammation in cardiomyocytes

Additional file 5. Original western blot gel images, related to Fig. 4

Additional file 3 of Three tyrosine kinase inhibitors cause cardiotoxicity by inducing endoplasmic reticulum stress and inflammation in cardiomyocytes

Additional file 3: Figure S12. Cell viability of NRCMs in response to afatinib, sorafenib, and ponatinib, related to Fig. 4. Figure S13. Low dose of TKIs induce ER stress over time in NRCMs, measured by mRNA fold changes, related to Fig. 4. Figure S14. Effects of ponatinib and sorafenib on heart weight, body weight, heart-to-body weight ratio, and Ddit3 expression in rat hearts, related to Fig. 4. Figure S15. Lipid peroxidation levels in NRCMs treated with cumene hydroperoxide and ethanol, related to Fig. 5. Figure S16. The effect of trolox on lipid peroxidation and ER stress induced by TKIs, related to Fig. 5. Figure S17. ISRIB and 4μ8c affected gene targets of Atf4 and Xbp1s induced by TKIs in NRCMs, related to Fig. 6. Figure S18. ISRIB and 4μ8c did not rescue NRCMs from cell death induced by the 3 TKIs, related to Fig. 6. Figure S19. The effects of ISRIB and 4μ8c on TKI-induced cell death examined using fluorescence imaging and quantification, related to Fig. 6. Figure S20. Persistent eIF2α phosphorylation up-regulated Nfkb1 and Il6 expression induced by 3 TKIs in H9C2 cells, but not Il1b or Tnf, related to Fig. 6

Additional file 2 of Three tyrosine kinase inhibitors cause cardiotoxicity by inducing endoplasmic reticulum stress and inflammation in cardiomyocytes

Additional file 2: Figure S1. EC50s of response calculated based on a four-parameter log-logistic model in the ATP fold change, related to Fig. 1. Figure S2. Seahorse experiment on acute effects of TKIs on mitochondrial oxygen consumption and extracellular acidification, related to Fig. 1. Figure S3. Mitochondrial membrane potential changes in response to TKIs observed by TMRE staining and its fold change, related to Fig. 1. Figure S4. Clustering of TKI-induced transcriptome data based on tSNE analysis, related to Fig. 2. Figure S5. Cluster 0, 2, 3, 4, 6 contained over 10 significant DEGs found by log2-based fold changes, related to Fig. 2. Figure S6. Expression of genes related to tRNA aminoacylation for protein translation in different clusters or in response to different drugs, related to Fig. 2. Figure S7. Good quality and consistency of 3’DGE-UMI RNA-seq, related to Fig. 2. Figure S8. The Jackstraw plot of the top 15 principal components in the tSNE analysis, related to Fig. 2. Figure S9. The number of unique genes, total counts, and proportion of mitochondrial DNA present in the 3'DGE-UMI RNA-seq data, related to Fig. 2. Figure S10. Correlation analysis between mitochondrial DNA and total counts or between unique genes and total counts in 3’DGE-UMI RNA-seq data, related to Fig. 2. Figure S11. Comparison of differentially expressed genes detected by 3'DGE-UMI and bulk RNA-seq for sorafenib and sunitinib treatments, related to Fig. 2

Additional file 4 of Three tyrosine kinase inhibitors cause cardiotoxicity by inducing endoplasmic reticulum stress and inflammation in cardiomyocytes

Additional file 4. Supplementary research methods and details on the reagent or resource used in the experiment