Figure 4

Effects of UK5099 and AZD7545 on BM EPCs stemness under normoxia and hypoxia, respectively. (A) Schema showing that the MPC inhibitor, UK5099, decreases pyruvate entry into the TCA cycle and that PDK inhibition by AZD7545 increases pyruvate oxidation. (B) Proliferation assay of BM EPCs treated with vehicle or various concentration of AZD7545 under hypoxia (n = 6). (C) Colony formation assay of BM EPCs treated with vehicle or 20uM AZD7545 under hypoxia (n = 6). (D) qRT-PCR showed lower expression of BM EPCs stemness markers in the presence of 20uM AZD7545 than with vehicle control under hypoxia (n = 5). (E) Representative experiment showing ECAR of BM EPCs and comparison of glycolytic rate and capacity in the presence or absence of AZD7545 under hypoxia (n = 6). (F) Representative experiment showing OCR of BM EPCs and comparison of basal and maximal respiration in the presence or absence of AZD7545 under hypoxia (n = 6). (G) Proliferation assay of BM EPCs treated with vehicle or various concentrations of UK5099 under normoxia (n = 6). (H) Colony formation assay of BM EPCs treated with 20uM UK5099 or vehicle under normoxia (n = 6). (I) qRT-PCR showed higher expression of BM EPCs stemness markers in the presence of 20uM UK5099 than with vehicle control under normoxia (n = 5). (J) Representative experiment showing ECAR of BM EPCs and comparison of the glycolytic rate and capacity in the presence or absence of UK5099 under normoxia (n = 6). (K) Representative experiment showing OCR of BM EPCs and comparison of basal and maximal respiration in the presence or absence of UK5099 under normoxia (n = 6). Data are presented as Mean ± SEM. *p < 0.05; **p < 0.01; ***p < 0.001 versus DMSO vehicle control.