Figure 1.
Network of differentially regulated metabolites.
Orange, Blue and Grey boxes indicate metabolites (mean of 5 replicates) upregulated, downregulated, and unchanged in cisplatin treatment, respectively (ANOVA p<0.01 and fold change 1.1); metabolites without a box were not detected. Numbers left (cisplatin) and right (control) under boxes indicate the corresponding intensities in MS-data. Results after 4 hours upper panel) and 8 hours (lower panel) are shown.
Figure 2.
Differentially regulated metabolic enzymes.
(A) Heatmap indicating metabolic enzymes obtained from Cytoscape metabolic signaling network (Fig. S4, highlighted in blue; Table S2), differentially regulated after 8 h of cisplatin treatment and enriched metabolic pathways within the dataset. (B) Regulation of metabolic enzymes by the transcription factor p53 obtained with Ingenuity pathway analysis.
Figure 3.
(A) Schematic representation of metabolomics and transcriptomics data integration leading to identification of common signaling networks related to nucleotide metabolism, SAMe pathways, polyamine pathways and urea cycle, and arginine & proline metabolism. (B) Integrated signaling network of metabolic enzymes and metabolites obtained with Ingenuity pathway analysis. Clusters of significantly enriched canonical pathways and related enzymes and metabolites are highlighted. Upregulated enzymes in green, downregulated enzymes in red. Upregulated metabolites in dark red, downregulated metabolites in blue.
Figure 4.
Upregulated enzymes in green, downregulated enzymes in red. Upregulated metabolites in dark red, downregulated metabolites in blue.
Figure 5.
Urea cycle and the metabolism of arginine and proline.
(A) Upregulated enzymes in green, downregulated enzymes in red. Upregulated metabolites in dark red, downregulated metabolites in blue. (B) Cell viability after knockdown of GFP (negative control), PRODH, PYCR2 or PARS2 in presence or absence of 5 µM cisplatin.
Figure 6.
Upregulated enzymes in green, downregulated enzymes in red. Upregulated metabolites in dark red, downregulated metabolites in blue.
Figure 7.
Upregulated enzymes in green, downregulated enzymes in red. Upregulated metabolites in dark red, downregulated metabolites in blue.