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. 2022 Jun 2;31(20):3458–3477. doi: 10.1093/hmg/ddac118

Figure 2.

Figure 2

EH301 affects nucleotide and amino acid metabolism and protects fibroblasts from thiol depletion stress. (A) Z score heatmap of metabolites significantly modified by EH301 in control, sALS1 and sALS2 fibroblasts (n = 6 per group), P-value < 0.05 after FDR adjustment. (B) Scatter plot of metabolic pathways enriched in control (square), sALS1 (circle) and sALS2 (triangle) fibroblasts after treatment with EH301, shape size reflects number of metabolites. (C) Percentage cell death in control, sALS1 and sALS2 fibroblasts grown in methionine/cystine depleted medium for 72 h and treated with EH301 or its single components (NR, PT). Bars represent average +/− standard error of mean of at least three independent experiments. One-way ANOVA followed by Fisher least significant difference (LSD). *P < 0.05, **P < 0.01, ****P < 0.0001. (D) Volcano plot of transcripts modified by EH301 in control fibroblasts (n = 3 per condition) grown for 48 h in methionine/cystine depleted medium compared to vehicle treatment. Red dots represent DEGs with log2 fold change greater than 1 with P-value < 0.05 after FDR adjustment. Some representative genes belonging to enriched GO pathways are labeled. (E) Significantly enriched pathways of upregulated and downregulated genes in control fibroblasts grown in methionine/cystine depleted medium for 48 h and treated with EH301 (n = 3 per condition).