Figure 5.

Elevated IL-6 Activates Pathways Associated With Oxidative Stress

(A) Forty-cytokine panel demonstrating elevations in interleukin (IL)-6, CXCL11, and CXCL13 (n = 2/group). (B) IL-6 enzyme-linked immunosorbent assay confirming statistically elevated plasma levels. Data were compared using a Mann-Whitney U test (n = 6/group). (C) Cardiac tissue western blots examining phosphorylated ERK1/2 (pERK1/2), total ERK1/2 (tERK1/2), phosphorylated STAT3 (pSTAT3), total STAT3 (tSTAT3), phosphorylated AKT (pAKT), total AKT (tAKT), AKT3, and GAPDH. (D) pERK1/2 was reduced in trametinib-treated animals. pSTAT3 and pAKT1/2 were elevated. Total protein changes were detected in STAT3 and AKT3. No changes in tERK1/2 and AKT1/2 protein were observed. Significant differences were observed in pERK1/2:tERK1/2, pSTAT3:tSTAT3, and pAKT:tAKT ratios. No difference was observed in pAKT:tAKT (n = 6/group). (E) Changes in mitochondrial genes were detected. Data are represented as z-scores in a heat map (n = 3/group). (F) Oxyblot analysis demonstrating increased protein carbonylation, a marker for oxidative stress, in trametinib heart lysate (n = 6/group).