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. 2019 Dec 23;8:e50163. doi: 10.7554/eLife.50163

Figure 7. Glycolysis inhibitors impair mitogenic effect of ErbB2 activation in cardiomyocytes.

(a) Cartoon showing the experimental procedure to analyse the effects of glycolysis inhibitors (2-DG and lonidamine) on cardiomyocyte proliferation. (b) Immunofluorescence analysis on P7 cardiac cultures derived from WT and caErbB2 OE hearts that are endogenously fluorescent for tdTomato under the MYH6 promoter, stained for the cell-cycle marker Ki67. Arrows point at Ki67+ CMs. (c) Quantification of % Ki67+ CMs from WT and caErbB2 OE derived from P7 cardiac cultures treated with the glycolysis inhibitors 2-DG (n = 4 for WT and n = 4 for OE), and lonidamine (n = 7 for WT and n = 4 for OE) or their diluents as controls. (d) Immunofluorescence analysis on P7 cardiac cultures derived from WT and caErbB2 OE hearts that are endogenously fluorescent for tdTomato under the MYH6 promoter, stained for the cytokinesis marker Aurora kinase B. Arrows point at Aurkb+ CMs. (e) Quantification of % Aurkb+ CMs from WT and caErbB2 OE derived from P7 cardiac cultures treated with the glycolysis inhibitors 2-DG (n = 4 for WT and n = 4 for OE), and lonidamine (n = 7 for WT and n = 4 for OE) or their diluents as controls. In all panels, bars represent the mean, and error bars represent s.e.m *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001, Scale bars represent 50 μm.

Figure 7.

Figure 7—figure supplement 1. Activation of ErbB2 signaling in murine MI model induces glycolytic gene expression while repressing mitochondrial genes.

Figure 7—figure supplement 1.

(a) Cartoon showing experimental procedure. Myocardial infarction (MI) was induced by left anterior descending coronary artery ligation at the same day when Dox was removed to induce cardiomyocyte specific caErbB2 overexpression (OE). Whole hearts where isolated for mRNA extraction 14 days after the MI and caErbB2 induction. (b) qPCR results with relative mRNA fold changes comparing wild type (WT, blue bars) with caErbB2 OE (OE, orange bars). Note the significant upregulation of glycolytic genes (Pfkp, Pdk3 and Pgk1) and significant downregulation of genes transcribed from the mitochondrial DNA (Mt-Nd1, Mt-Co2, Mt-Co1 and Mt-Co3). Bars represent mean values and error bars represent standard deviation. *p<0,05; **p<0,01; ***p<0001.