Figure 5
Influence of carnosine on MGO-induced differential gene expression. TNF-α stimulated HUVECS were exposed to 0 µM, 400 µM or 800 µM methylglyoxal (MGO) in the presence or absence of carnosine (CN, 20 mM) for 24 hours. Gene expression profiling was performed by microarray analysis. All pie charts depict, how many of a selected number of genes are synergistically/antagonistically regulated genes by CN + 800 µM MGO vs. only 800 µM MGO (both in presence of TNF-α). (A) The upper Venn-diagram displays differentially expressed genes (DEG, padj < 0.05, FC ≥ ±1.5 (up or down)) for the comparisons 800 µM MGO vs. 800 µM MGO + 20 mM CN and 0 µM MGO vs. 800 µM of MGO. The commonly shared differences (overlap) were further analyzed (arrow) and depicted as pie charts for CN counteracting the effect of MGO (antagonistic) or displaying a similar effect as MGO (synergistic). Note that all commonly shared differences found in the upper Venn-diagram were counteracted by CN (p < 0.01). (B) The upper Venn-diagram displays differentially expressed genes (DEG, padj < 0.05 irrespective of the fold change) for the comparisons 800 µM MGO vs. 800 µM MGO + 20 mM CN and 0 µM MGO vs. 800 µM of MGO. The commonly shared differences (overlap) were further analyzed (arrow) and depicted as pie charts for CN counteracting the effect of MGO (antagonistic) or displaying a similar effect as MGO (synergistic). Note that 95.5% of the commonly shared differences were counteracted by CN (p < 0.001). (C) The upper Venn-diagram displays differentially expressed genes (DEG, padj < 0.05, FC ≥ ±1.5 (up or down)) for the comparison 0 µM MGO vs. 800 µM of MGO only. The proportion of DEGs that was counteracted by CN in quantitative terms is displayed as pie chart. Note that 80.7% of the genes were regulated antagonistically (p < 0.0001). One-tailed binomial test was calculated to compare observed and expected frequencies.
